Exploring ancient and modern medical learning A Publication of Himalaya Wellness Company Probe Vol LXII No. 4 • Sep–Dec 2023 Quarterly • ISSN 0970-3039 Diabecon in the Management of Diabetic Retinopathy Liv.52 DS in the Management of Nonalcoholic Fatty Liver Disease The Effect of Insulin Resistance on the Pathogenesis of Polycystic Ovary Syndrome The Role of Vitamins and Minerals in Diabetes Mellitus The Milestones in the Discovery of Diabetes Mellitus Diabecon in the Management of Non–Insulin-Dependent Diabetes Mellitus Scan to read the e-version of Probe
Dosage Monotherapy: 1 tablet twice daily before food. Adjuvant therapy: 1 tablet once daily before food. The dosage may be titrated depending on the patient’s response. Diabecon DS–The beacon of hope for diabetics Diabecon DS (TABLET) The beacon of hope for diabetics In the management of type 2 diabetes… • Significantly reduces FPG, PPG, and HbA1c levels • In patients on sulfonylurea therapy - Helps in reducing the dosage - Prevents the development of tolerance - Reduces the risk of secondary failure • In patients on biguanide therapy - Improves peripheral utilization of glucose without adverse GI events • In patients on insulin therapy - Helps in reducing the dosage
Probe • Vol LXII • No. 4 • Sep–Dec 2023 • i Editorial Dear Doctor, The prevalence of diabetes mellitus has been rising at an alarming rate and continues to claim millions of lives every year, globally. World Diabetes Day (WDD)—observed on November 14, every year—is the world’s largest diabetes awareness campaign that reaches a global audience of over 1 billion to advocate the issues concerning diabetes care. This year’s WDD campaign is themed "Access to Diabetes Care" to ensure proper care and support to manage diabetes mellitus through education and medical provisions. One of the oldest known diseases, diabetes mellitus, was discovered in 81 AD. This issue of Probe brings to you an interesting feature that discusses the historic events, which that led to the discovery of diabetes mellitus, in the History of Medicine section. Excerpts from the preclinical and clinical trial reports that prove the efficacy of Diabecon, a phytopharmaceutical formulation from Himalaya Wellness Company, in the management of diabetes mellitus, are also featured in the EvidenceBased Insights section. Further, engaging articles such as the latest updates about the bidirectionality between insulin resistance and polycystic ovary syndrome; the significance of adequate nutrition in the management of diabetes mellitus; and the interrelationship between the altered gut microbiota and irritable bowel syndrome are also covered in this issue of Probe. We hope you find this issue’s collection of articles engaging and informative! — Editor
Probe • Vol LXII • No. 4 • Sep–Dec 2023 • iii Contents Evidence-Based Insights Diabecon . . . . . . . . . . . . . . . . . . . . . . . . . 2 Pilex . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Drug Alert . . . . . . . . . . . . . . . . . . . . . . . . . 12 From Other Pages Altered Gut Microbiota and Irritable Bowel Syndrome . . . . . . . . . . . . . . . . . . 14 Insulin Resistance and the Pathogenesis of Polycystic Ovary Syndrome . . . . . . . . . . . . . . . . . 16 Review - Journal and Online . . . . . . . . . . . . . . . . 18 Latest Research Safety and Efficacy of Liv.52 DS in the Management of Nonalcoholic Fatty Liver Disease . . . . . . . 20 Upcoming Events . . . . . . . . . . . . . . . . . . . . . 22 Abstracts From Literature . . . . . . . . . . . . . . . . . 24 History of Medicine . . . . . . . . . . . . . . . . . . . . 32 Herbal Notes Momordica charantia . . . . . . . . . . . . . . . . . . . 36 Gymnema sylvestre . . . . . . . . . . . . . . . . . . . . 38 Withania somnifera . . . . . . . . . . . . . . . . . . . . 39 Bauhinia variegata …… . . . . . . . . . . . . . . . . . . 40
iv • Probe •Vol LXII • No. 4 • Sep–Dec 2023 Editor: Dr Jayashree B Keshav Editorial Team: Shruthi VB, Shruthi VK, Harika GS, Shruthi M, Priyakshi M, Keerthini D, Harshitha C Layout Artists: Dayananda RS, Santosh G, Monesh NP For queries and other communications: The Editor—Probe Scientific Publications Division Himalaya Wellness Company Makali, Bengaluru 562162 Karnataka, India E-mail: publications@himalayawellness.com Copyright © 2023 Himalaya Wellness Company All content in this journal/publication is the property of Himalaya Wellness Company and is protected by Indian and international copyright laws. Any other use, including the reproduction, modification, distribution, transmission, republication, display, or performance, of the content in this journal/publication, without written permission from the owner, is strictly prohibited. For permission to reproduce articles/information published in this journal/publication, please write to publications@himalayawellness.com Nutrition Update The Role of Vitamins and Minerals in Diabetes Mellitus . . . . 42 Prescribing Information Diabecon (Tablet, DS Tablet) . . . . . . . . . . . . . . . . 46 Miscellaneous . . . . . . . . . . . . . . . . . . . . . . 52 Laughter, The Best Medicine Riddle Time Think Wise
Evidence-Based Insights
2 • Probe •Vol LXII • No. 4 • Sep–Dec 2023 Preclinical Evidence Diabecon® (TABLET, DS TABLET) Diabecon, a phytopharmaceutical formulation, is recommended for the management of diabetes and associated micro- and macrovascular complications. In newly detected type 2 diabetes, Diabecon, as a monotherapy, significantly reduces fasting plasma glucose, postprandial plasma glucose, and glycated hemoglobin levels. As an adjuvant to insulin or other oral hypoglycemic agents, Diabecon helps in reducing their dosage and prevents the development of tolerance. Effect of Diabecon® on Blood Sugar Level Aim To evaluate the effect of Diabecon on the blood sugar level (BSL) in normal rats and in alloxan-induced diabetic rats Materials and Methods This placebo-controlled study was conducted in male and female Wistar rats aged 2.5 to 3 months, weighing 175 to 250 g. The rats were divided into 2 groups: normoglycemic and alloxan-induced diabetic rats. In normoglycemic rats, 4 procedures were performed, and in alloxan-induced diabetic rats, 2 procedures were performed. Procedures in normoglycemic rats Effect of Diabecononblood sugar level Fifty normoglycemic rats were randomized into 2 groups (25 each). Group 1 (control) received 10 mL/kg body weight of water, and group 2 (test animals) received 2 g/kg body weight of Diabecon fine powder in the form of an aqueous suspension, once a day, orally, for 90 days. Fasting blood samples were collected to determine the blood sugar levels at baseline and after 30 and 90 days of treatment. Interactionwithadrenaline Fasting blood sugar (FBS) level was determined in 8 normoglycemic rats on day 0. Each rat was administered 100 µg of adrenaline subcutaneously, and the BSL was determined at 30, 60, 90, 120, 180, and 240 minutes. After basal blood sugar profiling was done post adrenaline administration, the rats were given Diabecon at a dosage of 2 g/kg, once a day, orally, for 21 days. Again, the FBS level was measured on day 21. Interactionwith tolbutamide In 6 normoglycemic rats, the FBS level was measured on day 0. Each rat received an aqueous suspension of tolbutamide at a dose of 250 mg/kg body weight, orally. The BSL was determined at every 1 hour for 4 hours following administration of tolbutamide. After basal blood sugar profiling was done post tolbutamide administration, the rats were administered an aqueous suspension of Diabecon at a dosage of 2 g/kg body weight, once a day, orally, for 21 days. The FBS level was measured on day 21. Interactionwith insulin The FBS level was measured in 8 normoglycemic rats on day 0. All rats were administered 0.25 IU of insulin intravenously, and the BSL was determined after 30, 60, 90, 120, 180, and 240 minutes. They were then administered Diabecon at a dosage of 2 g/kg body weight, once a day, orally, for 21 days. The FBS level was measured on day 21.
Probe • Vol LXII • No. 4 • Sep–Dec 2023 • 3 Effect of Diabecon on Blood Sugar Level Procedures in alloxan-induced diabetic rats Effect of Diabecononblood sugar andurine sugar levels The FBS level was analyzed in 16 female rats, and they were then administered alloxan monohydrate intravenously at a dose of 50 mg/kg body weight. Of the 16 rats, only 12 rats responded to alloxan monohydrate, and they were divided into 2 groups of diabetic rats (6 in each). Group 1 was given tap water at a dosage of 10 mg/kg body weight, once a day, orally, for 42 days, and group 2 was given Diabecon at a dose of 2 g/kg body weight. The FBS and fasting urine sugar level were monitored on day 20, 30, and 40. On day 42, the rats were killed to estimate the liver glycogen. Interactionwith insulin After confirmation of stable alloxan-induced hyperglycemia on day 8, 6 rats were administered 0.5 IU of insulin, intravenously. The BSL was determined at 30, 60, 90, 120, 180, and 240 minutes. Diabecon was administered at a dosage of 2 g/kg body weight, once a day, orally, for 21 days, and the BSL was analyzed at the same time periods. Results In normoglycemic rats • On day 30, the aqueous suspension of Diabecon exerted a significant hypoglycemic effect in both male and female rats (P < .005). There was no further decrease in the BSL after 90 days of treatment. • The hyperglycemic response to adrenaline was significantly reduced at 120 and 180 minutes following Diabecon administration (P < .05). • Tolbutamide decreased the BSL at the second hour and normalized it at the fourth hour, while treatment with Diabecon for 21 days decreased the BSL at the third and fourth hours (P < .05). • Treatment with Diabecon caused a decrease in BSL, similar to insulin, in normoglycemic rats. In alloxan-induced diabetic rats • Treatment with Diabecon caused a significant decrease in the FBS and urinary sugar level on days 20, 30, and 40 (Figure). Figure. The Mean FBS (mg%) Levels on Days 20, 30, and 40 Following Treatment With Diabecon in Alloxan-Induced Diabetic Rats FBS, fasting blood sugar. • In hyperglycemic rats, treatment with Diabecon significantly potentiated the hypoglycemic effect of insulin at 90, 120, 180, and 240 minutes. Conclusion The study findings suggest that Diabecon acts through several mechanisms. Treatment with Diabecon causes an improvement in insulin receptor responsiveness, leading to the enhanced uptake of glucose by tissues. Summary • The effects of Diabecon on blood sugar level (BSL) in normoglycemic rats and in alloxan-induced diabetic rats were evaluated in this study. • Four procedures were performed in normoglycemic rats, and 2 procedures were performed in alloxan-induced diabetic rats. • Diabecon exhibits a small but significant hypoglycemic effect in normoglycemic rats. • In hyperglycemic rats, treatment with Diabecon significantly potentiated the hypoglycemic effect of insulin. • In hyperglycemic rats, the hypoglycemic effect of insulin was enhanced, and the liver glycogen store was significantly higher following treatment with Diabecon. 400 200 100 300 Control Diabecon P < .05 0 Mean FBS, mg% Basal 72 h After Alloxan Day 20 Day 30 Day 40
4 • Probe •Vol LXII • No. 4 • Sep–Dec 2023 Clinical Evidence 1 Efficacy and Safety of Diabecon® in the Management of Non–Insulin-Dependent Diabetes Mellitus Aim To assess the efficacy and safety of Diabecon as a monotherapy and as an adjuvant with other oral hypoglycemic agents (OHAs) in the management of non–insulin-dependent diabetes mellitus (NIDDM) Materials and Methods This prospective, open, nonrandomized phase 3 trial included 50 patients of either sex (aged 30–60 y) who were diagnosed with NIDDM, and who were willing to give informed consent. Patients with insulin-dependent diabetes mellitus; those with NIDDM having acute complications of diabetes; patients with severe hypertension, myocardial infarction, cerebral vascular accident, renal failure, and a history of severe unstable angina; pregnant and lactating women; and patients who were not willing to give informed consent were excluded from the study. The patients were categorized into 2 groups (25 in each): group 1 had patients with recently diagnosed NIDDM who were not consuming any OHA, and group 2 had patients with NIDDM who were consuming OHAs. All patients were instructed to take 2 tablets of Diabecon, BID, for 3 months. The blood sugar level (BSL) was analyzed in each patient at the time of enrollment and every month for 3 months. All patients underwent biochemical laboratory examinations (hemogram; total leukocyte count; differential leukocyte count; blood urea; serum creatinine, albumin, and globulin levels; and lipid profile). The improvement in the NIDDM symptoms was evaluated using a predefined symptom score scale ranging from 0 to 3 (0, absent; 1, mild; 2, moderate; and 3, severe). The predefined primary end points were postprandial blood sugar level (PPBSL) control and reduction in the dose of other OHAs. The PPBSL control was graded as “excellent” (up to 130 mg%), “good” (up to 150 mg%), “fair” (up to 180 mg%), “poor” (up to 250 mg%), and “treatment failure” (> 250 mg%). The secondary end points were a reduction in the incidence of adverse reactions and overall compliance to the drug. All patients were followed up for 3 months, and response to Diabecon, subjective symptomatic relief, and changes in the symptom score for each symptom were recorded during each follow-up visit. Results In group 1, the fasting blood sugar level (FBSL) and PPBSL were significantly reduced by the third month. The FBSL reduced from 170 ± 40.47 to 161.51 ± 52.13 mg%, and the PPBSL reduced from 247.66 ± 70.65 to 223.13 ± 79.22 mg% (Figure 1). Group 2 patients experienced a significantly higher reduction in FBSL after 1 month (from 174.69 ± 55.77 to 148.66 ± 35.49 mg%), and it was further reduced to 145.40 ± 39.43 mg% by the end of the study (Figure 2). Overall, in both the groups, there were significant improvements in NIDDM symptoms such as polyuria and generalized weakness, and there was also an improvement in appetite. After 1 month of treatment, there was a significant reduction in leg cramps
Probe • Vol LXII • No. 4 • Sep–Dec 2023 • 5 Efficacy and Safety of Diabecon in the Management of Non–Insulin-Dependent Diabetes Mellitus and burning sensation (hands and soles) in both the groups. No clinically significant changes were observed in the hematological and biochemical parameters. No adverse reactions were reported, and the overall compliance to the treatment was excellent. Discussion The synergistic action of the ingredients of Diabecon shows beneficial effects in NIDDM. Gymnemic acids, active ingredients of Gymnema sylvestre, help correct the metabolic derangements in the diabetic liver, kidney, and muscle and reverse the pathological changes that occur during the hyperglycemic phase. Epicatechin, an active ingredient of Pterocarpus marsupium, possesses antihyperglycemic activity and also renormalizes the activities of hexokinase, glucokinase, and phosphofructokinase. Eugenia jambolana significantly reduces blood glucose, blood urea, and cholesterol levels. Boerhaavia diffusa significantly reduces glycosylated hemoglobin and increases the level of total hemoglobin. Tribulus terrestris inhibits gluconeogenesis and significantly reduces plasma triglyceride levels. Ocimum sanctum significantly lowers FBSL, uronic acid, total amino acid, total cholesterol, triglyceride, phospholipid, and total lipid levels. O sanctum renormalizes the glycogen concentration in various tissues. Conclusion Diabecon is safe and clinically effective as a monotherapy in patients with newly diagnosed NIDDM and as an adjuvant for patients using conventional OHAs. Summary • Fifty patients with non–insulin-dependent diabetes mellitus (NIDDM) were included in this study: 25 patients (group 1) had recently diagnosed NIDDM and were not consuming any oral hypoglycemic agent (OHA), and 25 patients (group 2) had NIDDM and were consuming OHAs. • All patients were advised 2 tablets of Diabecon, BID, for 3 months. • Both the groups showed a significant improvement in symptoms of NIDDM such as polyuria, generalized weakness, and loss of appetite. • The overall compliance to the treatment was excellent, with no adverse reactions. Figure 1. Reduction in Blood Sugar Level in Patients With Recently Diagnosed NIDDM and After Treatment With Diabecon Alone NIDDM, non–insulin-dependent diabetes mellitus. Figure 2. Reduction in Blood Sugar Level in Patients With NIDDM Consuming Conventional OHAs and Diabecon NIDDM, non–insulin-dependent diabetes mellitus; OHAs, oral hypoglycemic agents. 300 250 100 50 150 200 Fasting Postprandial 0 Blood Sugar, mg% Baseline Month 1 Month 2 Month 3 300 250 100 50 150 200 Fasting Postprandial 0 Blood Sugar, mg% Baseline Month 1 Month 2 Month 3
6 • Probe •Vol LXII • No. 4 • Sep–Dec 2023 Clinical Evidence 2 Effect of Diabecon® in the Management of Diabetic Retinopathy Aim To evaluate the effect of Diabecon in the management of diabetic retinopathy Materials and Methods This study included 30 patients with either non– insulin-dependent diabetes mellitus (NIDDM) or insulin-dependent diabetes mellitus (IDDM). Patients were graded according to the classification of diabetic retinopathy. They were monitored using modern diagnostic investigations such as direct/ indirect ophthalmoscopy, fluorescein angiography, and fundus photography. The patients were graded according to the Airlie House Classification and eye testing for diabetic retinopathy. All patients received Diabecon at a dosage of 2 tablets, TID, for 12 weeks, in addition to conventional antidiabetic treatment, and were followed up at intervals of 1 month, for 3 months. The mean symptom grades during each visit were noted and compared with the baseline symptom scores. Results The findings of this study suggest that there was a significant inhibition of microaneurysm; the mean grade in microaneurysm was 2.228 ± 4.084 before treatment and 0.466 ± 0.650 after 90 days of treatment with Diabecon (Figure 1). The mean grade of hemorrhage was 2.034 ± 0.815 before treatment and reduced to 0.866 ± 0.832 after treatment, thus, suggesting that Diabecon helps in resolving retinal and vitreous hemorrhage (Figure 2). The mean grade of exudates reduced from 2.034 ± 0.816 before treatment to 1.316 ± 0.81 after treatment (Figure 3). This significant reduction in exudation demonstrates the anti-inflammatory effect of Diabecon. The overall mean grade of retinitis proliferans reduced from 0.583 ± 0.925 before treatment to 0.550 ± 0.891 after treatment (Figure 4). Diabecon inhibited the proliferative changes in the retina and controlled progressive retina damage. The visual acuity of each patient was measured before and after administering Diabecon. On the Snellen chart, it was observed that 60% of the patients showed improvement in vision by at least one line. Funduscopic Figure 1. Effect of Diabecon on Microaneurysm in Diabetic Retinopathy 2.50 1.00 0.50 1.50 2.00 2.22 ± 4.08 0.46 ± 0.65 0 Mean Value Before Treatment After Treatment Figure 2. Effect of Diabecon on Hemorrhage in Diabetic Retinopathy 2.50 1.00 0.50 1.50 2.00 2.03 ± 0.81 0 Mean Value Before Treatment After Treatment 0.86 ± 0.83
Probe • Vol LXII • No. 4 • Sep–Dec 2023 • 7 Effect of Diabecon in the Management of Diabetic Retinopathy Syzygium cuminii, Tinospora cordifolia, and Ocimum sanctum have aldose reductase–inhibitory actions, and thus, prevent the acceleration of cataract formation in diabetics. Conclusion Diabecon is a safe and effective adjuvant in the management of retinopathy in diabetic patients. Summary • Thirty patients with non–insulin-dependent diabetes mellitus (NIDDM) and insulindependent diabetes mellitus (IDDM) were included in this study, and the patients were graded according to the classification of diabetic retinopathy. • All patients received Diabecon at a dosage of 2 tablets, TID, for 12 weeks, in addition to conventional antidiabetic treatment; they were followed up at intervals of 1 month, for 3 months. • Diabecon caused inhibition of microaneurysm, resolved retinal and vitreous hemorrhage, inhibited the proliferative changes in the retina and controlled progressive retinal damage, improved vision, and caused a considerable improvement in neovascularization and resolution of exudates. • The results suggest that Diabecon is a safe and effective adjuvant in the management of retinopathy in diabetic patients. Sources: Anturlikar SD, et al. Indian J Physiol Pharmacol. 1995;2(39):95–100. Kohli KR, et al. Antiseptic. 2004;101(11):487–494. Kant S, et al. Indian J Clin Pract. 2002;12(9):49–56. Figure 3. Effect of Diabecon on Exudates in Diabetic Retinopathy Figure 4. Effect of Diabecon on Retinitis Proliferans in Diabetic Retinopathy 2.50 1.00 0.50 1.50 2.00 2.03 ± 0.81 1.31 ± 0.81 0 Mean Value Before Treatment After Treatment 0.60 0.30 0.20 0.10 0.40 0.50 0.55 ± 0.89 0 Mean Value Before Treatment After Treatment 0.58 ± 0.92 examination revealed a considerable improvement in neovascularization and resolution of exudates. During the course of the study and after the withdrawal of Diabecon, no adverse effects were reported. Discussion Diabecon acts as an effective adjuvant to conventional oral hypoglycemic agents where the resolution of retinopathy is enhanced. Diabecon resolves, prevents, and retards retinal and vitreal microaneurysms and proliferative retinal changes. Curcuma longa, with its antioxidant and antiangiogenic actions, inhibits Ca2+ entry and protein kinase C activity, which helps prevent diabetic retinopathy. Gymnema sylvestre, Pterocarpus marsupium,
8 • Probe •Vol LXII • No. 4 • Sep–Dec 2023 Clinical Evidence 1 Pilex® (TABLET) Pilex Tablet is an Ayurvedic proprietary formulation recommended for the comprehensive management of hemorrhoids. Pilex Tablet has anti-inflammatory, analgesic, wound-healing, antimicrobial, hemostatic, laxative, and antioxidant actions. The ingredients of Pilex Tablet act synergistically to bring about a reduction in the hemorrhoidal mass and facilitate early resolution of symptoms such as rectal bleeding, pain, and itching, and correct chronic constipation associated with hemorrhoids. Efficacy of Pilex® in the Treatment and Management of External and Internal Hemorrhoids Aim To evaluate the efficacy and safety of Pilex Tablets in the treatment and management of mild-to-moderate external and internal hemorrhoids Materials and Methods This open-label, clinical study enrolled 50 patients (aged 22–63 y; both men and women), of whom 31 patients had external hemorrhoids, 10 patients had internal hemorrhoids, and 9 patients had both internal and external hemorrhoids. All patients received 1 Pilex Tablet, BID, for 6 weeks. Concomitant treatment with other hemorrhoidal drugs was discontinued during the study period. Proctoscopic examination was done before treatment and at every fortnightly follow-up during the treatment period. During the follow-ups, the patients were evaluated for the reduction in the size of the hemorrhoidal mass, pain during defecation, bleeding during defecation, anal pruritus, strenuous bowel movements, and loss of appetite. The intensity of the signs and symptoms was graded on a 4-point scale as 0, absent; 1, mild; 2, moderate; and 3, severe. At the end of the study, the efficacy of the treatment was recorded as either very good, good, or not effective. Results Thirty-two patients completed the treatment, while the remaining patients were lost to follow-up. Treatment with Pilex Tablets showed a significant reduction in the symptoms of hemorrhoids such as pain and bleeding and a significant improvement in the general health of the patients. The treatment response was recorded as very good in 56.25% of the patients and good in 37.50% of the patients. No side effects were observed during the study. Conclusion The results confirmed that Pilex Tablets are safe and effective in the treatment and management of mild-to-moderate internal and external hemorrhoids. The astringent, antiseptic, anti-inflammatory, and demulcent properties of Pilex Tablets helped reduce the pain and inflammation of hemorrhoids. The laxative property of Pilex Tablets helped relieve constipation associated with hemorrhoids. The antibacterial and astringent properties of Pilex Tablets helped prevent infection and healed the ulcers. Pilex Tablets also helped in shrinking the hemorrhoidal mass. Summary • This open-label clinical study enrolled 50 patients; 31 patients had external hemorrhoids, 10 patients
Probe • Vol LXII • No. 4 • Sep–Dec 2023 • 9 Pilex in the Management of External and Internal Hemorrhoids had internal hemorrhoids, and 9 patients had both internal and external hemorrhoids. • The patients received 1 Pilex Tablet, BID, for 6 weeks. • Proctoscopic examination was done before treatment and at every fortnightly follow-up during the treatment period. • The patients were evaluated for the reduction in the size of the hemorrhoidal mass, pain during defecation, bleeding during defecation, anal pruritus, strenuous bowel movements, and loss of appetite. • At the end of the study, the efficacy of the treatment was recorded as either very good, good, or not effective, based on a 4-point scale. • A significant reduction in the symptoms of hemorrhoids such as pain and bleeding was observed during the follow-ups. • The treatment response was very good in 56.25% of the patients and good in 37.50% of the patients. • No side effects were observed during the study. • The results demonstrate that Pilex Tablets are safe and effective in the treatment and management of mild-to-moderate internal and external hemorrhoids. Clinical Evidence 2 Efficacy of Pilex® in the Treatment and Management of Advanced Degrees of Hemorrhoids Aim To evaluate the efficacy of Pilex Tablets in the treatment and management of advanced degrees of hemorrhoids Materials and Methods This clinical study enrolled 11 patients, of whom 4 patients had third-degree hemorrhoids, and 7 patients had fourth-degree hemorrhoids. The duration of hemorrhoids in the patients varied from 3 months to 8 years. Prior to the study, the patients were operated upon for associated conditions such as acute retention of urine (due to benign prostatic hyperplasia), acute intestinal obstruction, perforated peptic ulcer, and obstructed inguinal hernia. Suprapubic transvesical prostatectomy was performed on patients with prostatic hypertrophy. Exploratory laparotomy was performed on patients with acute intestinal obstruction and perforated peptic ulcer for a simple closure of the perforation and release of the obstruction. The remaining patients were operated for hernia. Sphincter dilation of the anal canal was performed immediately after their respective surgical procedures. While still under the effect of anesthesia, the patients were turned to their left side and had their knees drawn up. The whole anal canal and lower rectum were slowly and uniformly dilated. Tight bands were broken down and irregularities in the anal canal were ironed out. The anal canal was then lightly packed with paraffin gauze to prevent prolapse of hemorrhoids. Pilex treatment was started 3 to 5 days after the surgery and sphincter dilation. The patients received 2 tablets of Pilex, TID, for 4 to 6 weeks. The patients also received an ounce of liquid paraffin at bedtime. After discharge, the patients were followed up
10 • Probe •Vol LXII • No. 4 • Sep–Dec 2023 Pilex in the Management of Advanced Degrees of Hemorrhoids fortnightly for assessing the regression of the hemorrhoidal mass and improvement in bleeding, pain, itching, discomfort, and proctoscopic findings, for 6 months. Results At the end of 6 to 8 weeks after the Pilex treatment, there was complete relief from pain, discomfort, and bleeding in all the patients. Complete regression of the hemorrhoidal mass was observed in 9 patients. Control of congestion and reduction in the size of the hemorrhoidal mass were also observed. All the patients were in good physical health during the follow-up period. Overall, a remarkable improvement in the symptoms of hemorrhoids was observed in the patients. Discussion The herbal ingredients of Pilex tablet such as Commiphora wightii, Berberis aristata, Bauhinia variegata, Mesua ferrea, and Blumea lacera have potent anti-inflammatory and analgesic actions. Azadirachta indica, B aristata, Acorus calamus, and Amorphophallus campanulatus have potent broad spectrum antimicrobial action. B aristata, Terminalia chebula, Mimosa pudica, and Mesua ferrea accelerate wound healing. T chebula, Terminalia bellirica, Cassia fistula, and Emblica officinalis are well known for their laxative action. These ingredients act synergistically to reduce varicosities of the venous plexus and also reduce the engorgement and turgidity of the veins and venous capillaries. Conclusion The results show that Pilex Tablets are effective in the treatment and management of advanced degrees of hemorrhoids. The herbal ingredients in Pilex Tablet act synergistically to bring about a reduction in the hemorrhoidal mass and facilitate early resolution of symptoms associated with hemorrhoids. Summary • The clinical study enrolled 11 patients (4 patients with third-degree hemorrhoids and 7 patients with fourth-degree hemorrhoids). • The patients were operated upon for acute retention of urine (due to benign prostatic hyperplasia), acute intestinal obstruction, perforated peptic ulcer, and obstructed inguinal hernia. • Sphincter dilation of the anal canal was performed immediately after their respective surgical procedures. • Pilex treatment was started 3 to 5 days after the sphincter dilation. The patients received 2 Pilex Tablets, TID, along with an ounce of liquid paraffin at bedtime, for 4 to 6 weeks. • The patients were followed up fortnightly for 6 months. • At the end of 6 to 8 weeks after the Pilex treatment, complete relief from pain, discomfort, and bleeding was observed in all the patients. • Complete regression of the hemorrhoidal mass was observed in 9 patients. • Control of congestion and reduction in the size of the hemorrhoidal mass were also observed. • The study results confirm the effectiveness of Pilex Tablets in the treatment and management of advanced degrees of hemorrhoids. Sources: Vastrad CS, Pakkanavar RV. Antiseptic. 2002;99(9):343–344. Belokar WK. Probe. 1979;18(2):109–112.
Dosage Tablet: 2 tablets twice daily till the symptoms are relieved, followed by 1 tablet twice daily as maintenance therapy. Directions for Use Ointment: Apply before and after evacuation of the bowel with the help of the applicator. Pilex–The medical answer to a surgical problem For the effective management of piles… For more than 75 years Pilex® (TABLET) The medical answer to a surgical problem Systemic therapy facilitates early resolution of symptoms – Helps control bleeding – Reduces venous engorgement – Relieves pain, irritation, and itching Pilex® forte(OINTMENT) The medical answer to a surgical problem Topical therapy promotes better healing – Offers local analgesic action – Controls bleeding, irritation, and itching – Facilitates smooth evacuation Duration of Therapy: Minimum 3 months
12 • Probe •Vol LXII • No. 4 • Sep–Dec 2023 DRUG ALERT Hyperuricemia, Gout, and Related Adverse Events AssociatedWith Antihypertensive Drugs The objective of this study was to comprehensively evaluate the association between various antihypertensive drugs and the occurrences of hyperuricemia, gout, and related adverse events (AEs), using the FDA Adverse Event Reporting System (FAERS). Open Vigil 2.1 was used to query the FAERS database. Hyperuricemia, gout, and related AEs were defined by 5 preferred terms: hyperuricemia, gout, gouty arthritis, gouty tophus, and urate nephropathy. Disproportionality analysis was performed, and a positive signal indicated an association between AEs and antihypertensive drugs. The numbers of antihypertensive drugs with positive signals for hyperuricemia, gout, gouty arthritis, gouty tophus, and urate nephropathy were 46, 66, 27, 8, and 6, respectively. These drugs included diuretics, antihypertensive drugs with central action, α-blockers, β-blockers, α- and β-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, renin inhibitors, vasodilators, and compound preparations. Furthermore, 42 antihypertensive drugs had positive signals for more than 1 AE. The study suggests that some potassium-sparing diuretics, calcium channel blockers, and losartan may be associated with an increased risk of hyperuricemia, gout, or related AEs, which is inconsistent with most previous studies. Moreover, the study also suggests that some antihypertensive drugs with central action, α- and β-blockers, renin inhibitors, and vasodilators may be associated with an increased risk of hyperuricemia, gout, or related AEs, which has not been reported in previous studies. These findings complement real-world evidence on the potential risks of hyperuricemia, gout, and related AEs associated with antihypertensive drugs. Source: Jiao XF, et al. Front Pharmacol. 2023;13:1045561. Increased Risk of Heart Failure in Elderly Patients TreatedWith BetaBlockers After AV Node Ablation Indication of b-blockers (BBs) in different scenarios in patients with cardiovascular disease is controversial. This study was conducted to evaluate the effect of BBs on survival and heart failure (HF) hospitalizations in a sample of pacemaker-dependent patients after AV node ablation to control ventricular rate for atrial tachyarrhythmias. This retrospective study included consecutive patients who underwent AV node ablation and was conducted in a single center between 2011 and 2019. The study’s primary end points were the incidence of all-cause mortality, first HF hospitalization, and the cumulative incidence of subsequent hospitalizations for HF. Competing risk analyses were employed. A total of 111 patients with a mean age of 73.9 years were included in the study, of which 74 patients (66.7%) were on BBs, and the remaining 37 patients (33.3%) were not on BB treatment. After a median follow-up of 45.5 months, 43 patients had died (38.7%), and 31 had been hospitalized for HF (27.9%). The recurrent HF hospitalization rate was 74/1000 patients/year. Patients treated with BBs had a nonsignificant trend toward higher mortality rates and a higher risk of recurrent HF hospitalizations (incidence rate ratio, 2.23; 95% confidence interval, 1.12–4.44; P = .023). These results demonstrated that after an AV node ablation, the use of BBs is associated with an increased risk of HF hospitalizations in a cohort of elderly patients. Source: Bertomeu-Gonzalez V, et al. Am J Cardiovasc Drugs. 2023;23(2):157–164.
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14 • Probe •Vol LXII • No. 4 • Sep–Dec 2023 Altered Gut Microbiota and Irritable Bowel Syndrome The gut microbiota that typically begins to colonize at birth, matures during the first 3 years of life. The gut is inhabited by more than 2000 different bacterial species of Bacteroidetes, Firmicutes, Actinobacteria, and Proteobacteria phyla.1 Healthy gut microbiota is essential for proper functioning of the gastrointestinal (GI) tract and is affected by factors such as dietary habits, smoking, anxiety, depression, and recurrent antibiotic treatments. A shift in the gut microbial diversity (gut dysbiosis) leads to the colonization of opportunistic pathogens. Several systemic studies have highlighted that the decreased abundance and diversity of the gut microbiota may increase the severity of irritable bowel syndrome (IBS) symptoms.1 IBS is one of the most common GI diseases that manifests as abdominal pain, bloating, and mixed bowel movements of diarrhea and/or constipation. The pathophysiology of IBS is intricate and multifactorial. Alterations in the gut–brain axis, abnormalities in the gut endocrine cells and the enteric nervous system, visceral hypersensitivity, GI dysmotility, postinfection status and low-grade inflammation, malabsorption of carbohydrates, and altered gut microbiota composition are found to influence IBS.1 Influence of the Gut Microbiota on GI Health Diminished fecal microbial diversity and altered gut flora in patients with IBS suggest a causal involvement in the development and recurrence of IBS.2 Studies confirm that the fecal microbiota in patients with IBS differs significantly from that in healthy individuals, and it potentially contributes to alterations in bowel habits and affects colonic transit. The gut metabolome, intestinal permeability, and inflammatory pathways have also been suggested to play a role in microbiota-related GI diseases.3 Gut microbiota signatures of IBS Reduced diversity of the gut microbiota and presence of Clostridium, Prevotella, and methanogenic bacterial species are considered as IBS-specific microbiome signatures that associate with the severity of symptoms.3 Postinfection IBS, small intestine bacterial overgrowth, stress, antibiotics, diet, and early childhood feeding and hygiene practices influence the gut microbiota and affect the incidence rate of IBS. A gut microbiota analysis suggested a doubled ratio of Firmicutes to Bacteroidetes; abundance of Dorea, Ruminococcus, and Clostridium species; and fewer Faecalibacterium species in patients with IBS compared with that in healthy controls.4 The Importance of Prebiotics and Probiotics Pre- and probiotics are nonpharmacologic recommendations for reducing the symptoms and severity of IBS. Consumption of prebiotics provides essential nutrients to enhance the growth of beneficial bacteria and deters the pathogens in the bowel. Consumption of probiotics can normalize the interaction between pro- and anti-inflammatory cytokines; stabilize the microbiota; and reduce visceral sensitivity, intestinal permeability, and inflammation.1,2 References 1. Mazzawi T. Microorganisms. 2022;10(7):1332. 2. Sharma S, et al. Cureus. 2023;15(3):e36565. 3. Ghaffari P, et al. J Transl Med. 2022;20:173. 4. Olyaiee A, et al. Front Med. 2022;9:890127.
FOOD FOR SPECIAL DIETARY USE - Supports gut health and helps in symptomatic relief from Irritable Bowel Syndrome in adults. Keep out of the reach of children. NOT FOR MEDICINAL USE. Not for parenteral use. To be used under the medical advice of a health care professional. Pregnant, nursing and lactating women or infants, children under 5 years, adolescents and the elderly should consult a health care professional before use. Do not exceed the recommended daily usage. Florasante™ (CAPSULE) Prebiotic and probiotic for improved gut health Now available in Pack • A synbiotic with botanical extract advantage for irritable bowel syndrome (IBS) • Contains both spore-forming and thermotolerant strains– Proven efficacy in gut health • Is clinically tested for symptoms in IBS • Unique capsule-in-capsule technology and Activ-Vial pack offer better stability and viability of probiotics. • Is stable at room temperature and does not require refrigeration In irritable bowel syndrome... Dosage: 1–2 capsules twice daily. Indication: Irritable bowel syndrome Florasante–Prebiotic and probiotic for improved gut health
16 • Probe •Vol LXII • No. 4 • Sep–Dec 2023 Insulin Resistance and the Pathogenesis of Polycystic Ovary Syndrome Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders, globally affecting more than 20% of women in their reproductive age. PCOS is a heterogeneous condition characterized by hyperandrogenism, polycystic ovary morphology, and dysfunctional ovulation. Scientific data confirm that most women with PCOS are metabolically resistant to insulin. More than 65% of women with PCOS have insulin resistance (IR) and compensatory hyperinsulinemia. IR has been identified in all 4 phenotypes of PCOS— type A: a combination of polycystic ovary (PCO), chronic oligo-anovulation (OA), and hyperandrogenism (HA); type B: a combination of OA and HA; type C: a combination of PCO and HA; and type D: a combination of PCO and OA. IR is predominantly identified in the classical phenotypes (types A and B) of PCOS (80%). IR—an impaired insulin response in skeletal muscle, hepatic, and adipose tissues—is predominantly due to a defective glucose transport system (glucose transporter type 4) across the plasma membrane. In PCOS, IR occurs due to a disruption in downstream signal transmission from the insulin receptor—a postreceptor abnormality. Thus, women with PCOS exhibit a pronounced unresponsiveness and insensitivity to insulin stimulation in tissues. Bidirectionality Between IR and PCOS In PCOS, the sequence of events begins with IR as the primary contributor, leading to compensatory hyperinsulinemia to maintain normal glycemia. A considerable period during the progression of PCOS is also marked by supraphysiologic insulin levels that may • directly or indirectly disrupt the ovarian function, • stimulate enhanced production of androgens, and • promote the arrest of preantral follicle development. This depicts a bidirectional link between IR and PCOS. The clinical presentation of PCOS is influenced by other insulin-related systemic effects. Women with PCOS and IR are at a significantly increased risk of adverse pregnancy outcomes and chronic diseases such as type 2 diabetes mellitus, cardiovascular diseases, and metabolic syndrome, which thereby seriously affect their physical and psychological health. Therefore, identifying the risk factors that influence the development of IR in PCOS, accurate assessment of insulin sensitivity in the early stages of PCOS, and effective medical intervention for IR in women with PCOS are essential to reduce the risk of long-term complications. Lifestyle modifications are considered a cornerstone in the management of IR in women with PCOS. Implementing calorie-restricted dietary plans and aerobic physical exercise in daily routine may help improve insulin sensitivity in women with PCOS. Sources: Herman R, et al. Int J Mol Sci. 2023;24(4):3140. Zhao H, et al. J Ovarian Res. 2023;16:9.
Evecare forte™ (LIQUID, TABLET) • Regularizes endogenous hormone levels • Helps reduce the number of abnormal follicles – Corrects the cyclical rhythm • Helps in restoring ovulation – Improves fer tility rate • Insulin-sensitizing activity corrects ovarian dysfunction and other metabolic derangements associated with insulin resistance • Safe, polyherbal, and nonhormonal menstrual modulator In PCOS... Dosage Liquid: 2–4 teaspoonsful (10–20 ml) twice daily for 3 to 6 months. Tablet: 1 tablet twice daily for 3 to 6 months. Indication: PCOS Evecare forte–
18 • Probe •Vol LXII • No. 4 • Sep–Dec 2023 Journal Journal of Orthopaedics and Traumatology The Journal of Orthopaedics and Traumatology is an open-access peer-reviewed journal, published by SpringerOpen. It is the official journal of the Italian Society of Orthopaedics and Traumatology. It publishes original research papers, systematic reviews, brief communications, case reports, and letters to the editor, with topics pertaining to the field of orthopedic and traumatological surgery. The aim of this publication is to provide an international forum for discussion and exchange of ideas on various topics related to orthopedics and musculoskeletal trauma. REVIEW Online International Diabetes Federation https://idf.org/who-we-are.html The International Diabetes Federation (IDF) has been leading the global diabetes community since 1950. IDF is an umbrella organization of more than 240 national diabetes associations in 160 nations and territories. The federation’s initiatives aim to influence policies, promote public awareness, encourage health improvement, contribute to the exchange of high-quality information regarding diabetes, and educate people with diabetes and health care providers. The mission of IDF is to enhance the lives of diabetic patients and prevent diabetes in those who are at risk. IDF is in official relations with the WHO and is associated with the Department of Public Information of the United Nations. Image source: https://jorthoptraumatol. springeropen.com/about
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20 • Probe •Vol LXII • No. 4 • Sep–Dec 2023 Safety and Efficacy of Liv.52® DS in the Management of Nonalcoholic Fatty Liver Disease Gontar Siregar1, Rangesh Paramesh2, Rajesh Kumawat2, Palaniyamma D2, Srikrishna HA2 Eur J Clin Exp Med. 2021;19(2):129–136. Authors’ Affiliations 1Division of Gastroenterology-Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Sumatera Utara, Medan, Indonesia 2Himalaya Wellness Company, Makali, Bengaluru, India Aim To assess the safety and efficacy of Liv.52 DS tablets in the management of nonalcoholic fatty liver disease (NAFLD) Materials and Methods This prospective interventional study included 60 patients of both sexes (aged 18–65 y) who were diagnosed with NAFLD through clinical examination, laboratory testing, and ultrasound findings, and those who were willing to provide informed consent. A detailed medical history and symptom evaluation were performed at the first visit. Additionally, the patients were examined for the presence of steatohepatitis with hepatomegaly. All patients received 2 Liv.52 DS tablets, BID, for 2 months. The patients were subjected to liver function tests (LFTs) including aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase, gamma-glutamyl transferase, serum bilirubin, and albumin; ultrasonic evaluation for hepatomegaly analysis; and NAFLD score assessment to determine the severity of fibrosis due to NAFLD, at baseline and at the end of months 1 and 2. Statistical analysis was performed using GraphPad Prism software version 6.07 for Windows (GraphPad Software, CA, USA). The data about LFTs, biochemical investigations, and NAFLD scores were analyzed Table 1. Effect of Liv.52 DS on Liver Fibrosis (NAFLD Fibrosis Score) Scale N Baseline Month 1 Month 2 NAFLD Score < − 1.455 = F0–F2 33 Mean − 2.886 − 2.911 − 2.915 SD 1.044 1.061 0.8617 NAFLD Score − 1.455 – 0.675 = Indeterminate Score 27 Mean − 0.650 − 0.684 − 0.849 SD 0.484 0.543 0.667 NAFLD Score > 0.675 = F3–F4 0 0 0 0 Statistical test: ANOVA followed by Tukey’s multiple comparison test; values are represented as mean ± SD. Formula for NAFLD Score: − 1.675 + 0.037 × age (y) + 0.094 × BMI (kg/m2) + 1.13 × IFG/diabetes (yes = 1, no = 0) + 0.99 × AST/ALT ratio - 0.013 × platelet (× 109/L) − 0.66 × albumin (g/dL). NAFLD score was evaluated: NAFLD score < − 1.455 = F0–F2; NAFLD score − 1.455 to .675 = indeterminate score; NAFLD score > .675 = F3–F4. ALT, alanine transaminase; AST, aspartate transaminase; IFG, impaired fasting glucose; NAFLD, nonalcoholic fatty liver disease. using ANOVA followed by Tukey’s multiple comparison test. Results It was observed that there was a reduction in the liver fibrosis score at month 1, and there was a further reduction in the score by month 2. Similarly, patients with indeterminate scores also demonstrated a reduction in the fibrosis score after treatment with Liv.52 DS. This indicates the positive effect of Liv.52 DS in reducing NAFLD-associated liver fibrosis (Table 1). At baseline, 75% of the patients exhibited hepatomegaly (liver size > 16 cm), and 25% of the patients showed no hepatomegaly (liver size
Probe • Vol LXII • No. 4 • Sep–Dec 2023 • 21 Safety and Efficacy of Liv.52 DS in the Management of Nonalcoholic Fatty Liver Disease Table 2. The Effect of Liv.52 DS on Hepatomegaly Liver Size on Ultrasonographic Screening Patients, n (%) Baseline Month 1 Month 2 > 16 cm (Hepatomegaly) 45 (75) 43 (72) 25 (42) < 16 cm (No Hepatomegaly) 15 (25) 17 (28) 35 (58) Table 3. Effect of Liv.52 DS on LFTs (AST and ALT) Parameter , IU/L Baseline Month 1 Month 2 AST 60.33 ± 13.04 56.43 ± 15.47 54.12 ± 17.26 P < .0339a ALT 70.68 ± 18.49 64.13 ± 22.07 P < .0215a 61.9 ± 22.7 P < .0022a Statistical test: ANOVA followed by Tukey’s multiple comparison test. Significance was fixed at P < .05. Values are represented as mean ± SD. aCompared with baseline. LFTs, liver function tests; AST, aspartate transaminase; ALT, alanine transaminase. high-density lipoprotein and low-density lipoprotein levels were within the normal range, the total serum cholesterol and serum triglyceride levels were borderline high at screening, and they remained the same at the end of the study. There were no adverse events reported during the entire study period. The overall compliance with the treatment was good, with no treatment discontinuation. Discussion The significant hepatoprotective activity seen in this study can be attributed to the synergistic action of the bioactive herbs present in Liv.52 DS—Capparis spinosa, Cichorium intybus, Solanum nigrum, Terminalia arjuna, Cassia occidentalis, Achillea millefolium, and Tamarix gallica. C spinosa acts against chemically induced hepatotoxicity and prevents elevation of malondialdehyde (plasma and hepatic), AST, and ALT levels. C intybus suppresses the oxidative degradation of DNA in tissue debris. S nigrum protects the DNA against oxidative damage and acts as a potent scavenger of hydroxyl and diphenylpicrylhydrazyl radicals. T arjuna reduces cholesterol levels. C occidentalis modulates hepatic enzyme levels, which provides hepatoprotection. T gallica acts as a hepatic stimulant and has a beneficial effect on liver glycogen and serum proteins. Conclusion The results of this study reveal that after treatment with Liv.52 DS, there was a significant improvement in hepatomegaly and liver function parameters such as AST and ALT. During the study period, there was no progression of liver fibrosis due to NAFLD. Also, no adverse events were reported by the patients. The hematological and biochemical findings of this study suggest that Liv.52 DS is effective and safe in the management of NAFLD. Figure. Effect of Liv.52 DS on Liver Size by Ultrasound Measurement 0.7 0.5 0.2 0.1 0.3 Baseline Month 1 Month 2 0.4 0.6 Hepatomegaly (> 16 cm) No Hepatomegaly (< 16 cm) 0.8 0 Patients, % 0.75 0.72 0.42 0.25 0.28 0.58 < 16 cm). Whereas, after 2 months of treatment with Liv.52 DS, only 42% of patients exhibited hepatomegaly, and 58% of patients showed no hepatomegaly (Table 2). After treatment with Liv.52 DS, the liver size significantly reduced from 17.44 ± 1.9 cm at baseline to 17.29 ± 1.77 cm at the end of 1 month (P < .0001) and further reduced to 15.87 cm at the end of month 2 (Figure). Also, the levels of ALT and AST were elevated at baseline and decreased at the end of the study (Table 3). Hematology and biochemical investigations showed that Liv.52 DS is a safe formulation. Though
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