A Hospital Based Observational Study to Detect Non-Alcoholic Steatohepatitis by Acoustic Radiation Force Impulse in Individuals with Diabetes Mellitus and Metabolic Syndrome.

Non-alcoholic fatty liver disease (NAFLD)/ non-alcoholic steatohepatitis (NASH) is a rising epidemic with a potential for life threatening complications, especially in individuals with diabetes mellitus (DM) and metabolic syndrome. Though liver biopsy remains the recommended gold standard for diagnosing liver fibrosis, due to its technical feasibility and requirement of trained personnel, methods to develop non-invasive diagnostic tools for liver fibrosis have recently been underway. One such non-invasive method to diagnose liver fibrosis, point shear wave elastography using Acoustic Radiation Force Impulse (ARFI)-Imaging has gained remarkable results. This research was carried out to assess non-alcoholic steatohepatitis by acoustic radiation force impulse in individuals with diabetes and metabolic syndrome. Between March 2020 and October 2021, 140 patients with DM and metabolic syndrome, were identified. Demographic profile as well as reports of complete blood count, liver function tests, renal function tests, serum lipid profile, fasting blood sugar and postprandial blood sugar of the study participants were collected and recorded. Point shear wave liver elastography using ARFI imaging was performed for each of the study participant. NAFLD fibrosis score was determined in all of the study participants using appropriate software. Continuous and categorical variables were expressed as mean ± standard deviation and percentages respectively. Two-sided p values were considered as statistically significant at p value <0.05. Chi square test was done to see the association of clinical symptoms with fibrosis or non fibrosis. Independent t test was done to compare test variables and lab parameters between fibrosis and no fibrosis. Among the 140 study participants, 83 were males (59.29%) and 57 were (40.71%) females. On analysing the mean velocities measured by using ARFI elastography,30 participants (21.43%) had mean velocities >2.2m/s suggesting the presence of liver fibrosis and 110(78.57%) participants had mean velocities <2.2m/s did not have fibrosis. Among 83 males, 20(24.1%) had fibrosis and among 57 females, 10(17.5%) had fibrosis (p>0.05). Mean age of the 'Fibrosis' group was 54.53 (SD12.42) and that of the 'No fibrosis' group was 56.20(SD 11.76). Majority of the participants were between 56 and 65 years of age (50 participants). The mean height, weight and BMI of the 'Fibrosis' group was 152.84(±41.29), 73.33(±8.41), and 27.37(±2.73) respectively and that of the 'No fibrosis' group was 157.31(26.47), 70.89(12.46) and, 27.10(4.22) respectively (p>0.05). In the 'Fibrosis' group, majority (60%) were in the Obese 1 group and in the 'No fibrosis' group as well, majority were in the Obese 1 group (47.3%) (p=0.286). The mean (±SD) NAFLD- fibrosis Score was -1.54±1.06 in the 'No fibrosis' group and -0.61±1.81 in the 'Fibrosis' group (p value=0.012). There was no significant difference between fasting blood sugar, postprandial blood sugar, triglyceride and HbA1c levels among the 'Fibrosis' and 'No Fibrosis' groups. Among the 2 groups, there was no statistically significant difference between waist circumference, presence of hypertension, dyslipidaemia or other co-morbidities, in our study. None of the 30 individuals in the 'Fibrosis' group were on insulin (p=0.032), showing a significant difference in insulin usage among the 2 groups. There were significantly higher mean values of NAFLD-Fibrosis score in the individuals with fibrosis as compared to those with no fibrosis (p<0.05). NAFLD, diabetes mellitus and metabolic syndrome are part of the same spectrum. Individuals with diabetes mellitus and metabolic syndrome have a higher risk of developing liver fibrosis. Though in our study, parameters such as age, gender, hypertension, deranged blood sugars and lipid profile values were not significantly associated with liver fibrosis, NAFLD fibrosis score was found to have a significant association with liver fibrosis in these individuals.

Changes in Peripheral Brachial Blood Pressure from Supine to Lateral Decubitus Position in Hypertensive and Normotensive Subjects.

Arterial blood pressure is crucial for supplying the nutritional demands of the all body tissues and is also under tight control for the same. The day to day stress impacts the blood pressure (BP), which is effectively corrected by the baroreceptors mechanism. The effect of lateral decubitus position on the blood pressure with respect to supine position needs to be evaluated as it impacts the haemodynamics. The peripheral brachial blood pressure changes are studied among the normotensives and hypertensives with its significance from change in supine to lateral decubitus position. Sixty (60) normotensives and 60 hypertensive subjects were evaluated for arterial blood pressure measurement using mercury sphygmomanometer by gold standard auscultatory method in the supine, right and left lateral decubitus position. The same observer measured the blood pressure at the similar point of time for all the participants. The Supine and lateral decubitus Systolic and diastolic blood pressure (Mean±SD) parameters were recorded and compared using the paired 't' test (Supine Normotensives SBP 112.5±16.9, DBP 70.1±17.7 mm of Hg; Hypertensives Stage I SBP 130.2±14.5, DBP 85.2±2.8 mm of Hg; Hypertensive Stage II SBP 152.6 ±17.5, DBP 98.4±9.5mm of Hg). The mean and percentage change in systolic and diastolic BP for Normotensives from supine to right lateral position- SBP 11.6 mm of Hg (10.3%), DBP 8.8 mm of Hg (12.5%) and supine to left lateral position SBP 12.5mm of Hg (11.1%), DBP 9.9 mm of Hg (14.1%) p<0.05, for Hypertensives Stage I supine to right lateral position SBP 13.8 mm of Hg (10.5%), DBP 14.8 mm of Hg (17.37%) and supine to left lateral position SBP 13.5 mm of Hg (10.3%), DBP 12.3 mm of Hg (14.13%) p<0.05 and for Hypertensive Stage II from supine to right lateral position SBP 22.6 mm of Hg (14.8%), DBP 16.6 mm of Hg (16.8%), form supine to left lateral position SBP 12.3mm of Hg (8%), DBP 14.7mm of Hg (14.9%) p<0.01) changed significantly among the all the groups with respect to change from supine to lateral decubitus position. The fall in diastolic BP was of greater magnitude than the systolic BP. The right lateral decubitus position was dominant among the hypertensives for producing the change as compared to left lateral decubitus position. However among the normotensives it was left lateral decubitus which produced greater reduction in blood pressure. The lateral decubitus position definitively reduces the blood pressure as compared to supine position and the changes produced can't be simply ascribed to the hydrostatic effect of gravity on blood column. Sleeping on lateral side could thus be advantageous in reducing the arterial blood pressure.

Atypical presentations of cutaneous tuberculosis: Series of 10 cases.

Cutaneous tuberculosis classically presents as Lupus vulgaris, scrofuloderma, tuberculosis verrucose cutis and tubercular abscess. Hypersensitivity reaction to the bacilli leads to Lichen scrofulosorum and papulonecrotic tuberculids. At the same time, it can have myriad of clinical presentations, many of which are still undescribed. It is important to regularly update ourselves with these unusual manifestations so as to ensure early treatment and reduction of overall morbidity. In this case series tuberculosis manifesting as rapidly progressing diffuse facial granulomas, sporotrichoid tuberculosis, tuberculosis mimicking squamous cell carcinoma, scrofuloderma as tubercular ulcer, lupus vulgaris with nasal septal perforation, lupus vulgaris resembling furuncle, psoriasis, dermatitis and BT Hansen are described in immunocompetent individuals. These cases highlight the importance of recognition of atypical forms of cutaneous tuberculosis to minimize scarring and dissemination of bacilli.

The Significance of ERG and Androgen Receptor Expression in Adenocarcinoma Prostate.

Background Fusions of transmembrane protease, serine 2 (TMPRSS2) with erythroblast transformation specific transcription factors have been found in prostate cancer. The v-etserythroblastosis virus E26 oncogene homologue (ERG) is a proto-oncogene of the erythroblast transformation specific transcription factor family. TMPRSS2-ERG fusion is the most common molecular alteration present in about 50% of prostatic adenocarcinomas. Androgen receptor (AR) plays a key role in prostate development and is involved in the progression of prostate cancer. Objective To evaluate the significance of combined ERG and AR expression in cases of prostatic adenocarcinoma. Method The study was conducted at Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India. Formalin fixed-paraffin embedded archival prostatic tissue specimens were obtained. A total of 10 cases of prostatic adenocarcinoma were included in the study. Immunohistochemistry for Androgen receptor was done by the standard protocol. Multiplex immunohistochemical staining was done for ERG+CK5 using a primary antibody cocktail of mouse and rabbit antibodies. Result Specific AR immunostaining was exclusively nuclear and was present in all 10 cases in varying intensity. Specific ERG immunostaining was nuclear and was present in seven cases (70%) and absent in three cases (30%). The three cases that were negative for ERG had a Gleason score of ≤ 6 and the AR staining was strong and present in about 90% of the cells. Gleason score was directly related to the ERG staining while AR staining was inversely related to the ERG staining. Conclusion The prognostic value of combined ERG and AR over-expression, its associated genes should be further investigated as potential therapeutic targets in prostate cancer progression. Preliminary data is being presented. Larger prospective studies with survival analysis are essential for prognostic significance.

Immunoglobulin M nephropathy nephropathy in adults and adolescents in India: a single-center study of natural history.

BACKGROUND: Immunoglobulin M nephropathy (IgMN) is an idiopathic glomerulonephritis (GN) usually presenting clinically as steroid resistant/dependent nephrotic syndrome (NS) with pathology of mesangial proliferative GN or focal and segmental glomerulosclerosis with diffuse predominant mesangial IgM deposits. Not much information is available about its natural history. This is the first Indian study to our knowledge on IgMN in adults and adolescents. MATERIALS AND METHODS: We evaluated renal biopsies performed at our center between January,'04 to September,'09. Biopsies of all adolescents and adults were evaluated for IgMN and we studied their age, gender distribution, blood pressure (BP), disease duration, steroid/immunosuppressive management and serial serum creatinine (SCr), urinary proteins, and BP values. Patients with other systemic diseases/infections and children were excluded. RESULTS: IgMN constituted 4.3% of 2702 adult renal biopsies. No significant gender predilection was noted. Males presented at average age of 23.1 years, females at 30 years. Steroid-dependent NS was the commonest presentation noted in 75% followed by steroid-resistant NS. Hypertension was noted in 10% patients. Mesangial proliferative GN (MePGN) was commonest histopathological finding noted in 74.4%, followed by focal segmental glomerulosclerosis (FSGS) in 16.2%, and minimal change disease (MCD) in 9.4% biopsies. Sole IgM deposits were noted in 88.5%. All MCD, 35.6% MePGN reached remission, FSGS progressed to renal failure by 1 year. Hypertension, proteinuria, interstitial fibrosis, and FSGS were bad prognosticators. CONCLUSIONS: This is the first Indian study of IgMN in adults and adolescents carried out over a period of 5.8 years, which has shown that hypertension, proteinuria, and interstitial fibrosis at presentation have bad prognosis.

Preliminary pharmacological evaluation of Martynia annua Linn leaves for wound healing.

OBJECTIVE: To evaluate the wound healing potential of fractions from ethanol extract of Martynia annua (M. annua) Linn leaves. METHODS: Ethanol extract of M. annua Linn leaves was fractionate into three different fractions (MAF-A, MAF-B and MAF-C) which were screened for wound healing potential using two models: excision and incision on rats. The thin layer chromatography (TLC) profile of all fractions were analyzed and TLC of luteolin was also done. The Povidone-Iodine Ointment was used as reference for comparision. Excision and incision wounds were created on dorsal portion of rats for study. Wound contraction, biochemical parameters (protein level and hydroxyproline level) and histopathological study were performed in excision wound model whereas incision model was used for determination of tensile strength. RESULTS: The wound contraction and tensile strength of skin tissues were observed significantly greater in MAF-C fraction treated group than other two fractions (P<0.01). In excision wound method (on day 18) protein content and hydroxyproline were found significantly higher in MAF-C group than control group (P<0.01). Histopathological study also showed better angiogenesis, matured collagen fibres and fibroblast cells as compared with the control group. CONCLUSIONS: In conclusion, our findings suggest that fraction MAF-C from ethanol extract of M. annua leaves is found most effective in wound healing.

Nephroprotective activity of Momordica dioica Roxb. in cisplatin-induced nephrotoxicity.

In this study, the ethanol extract of Momordica dioica fruit extract (200 mg kg(-1)) was studied for nephroprotective and curative activities. Chloroform, ethyl acetate, ethanol and aqueous extracts were prepared. In vitro antioxidant activity was made the basis for the selection of the ethanol extract for further studies. In DPPH free radical scavenging activity, the ethanolic extract has shown maximum inhibition (84.2%), followed by aqueous (74.8%), ethyl acetate (69.4%) and chloroform (59.7%) extract. On the other hand, in total antioxidant activity, the ethanol extract has shown 80.1% inhibition, followed by aqueous (71.9%), ethyl acetate (67.2%) and chloroform (53.2%) extracts. A single dose (5 mg kg(-1), i.p.) of cisplatin was administrated to induce nephrotoxicity. Blood urea and serum creatinine were analysed as biochemical markers of nephrotoxicity. Reduced glutathione (GSH) and the product of lipid peroxidation (MDA) were also measured in kidney tissues. A single dose of cisplatin resulted in significant reduction in body weight and increased the urea and creatinine levels. Extract administration has shown significant recovery in the levels of these biochemicals in curative (p < 0.001) and protective groups, whereas a single dose of cisplatin caused significant reduction in GSH and an increase in malondialdehyde production. Recovery was observed in treated groups. This study suggested that the nephroprotective and curative activities of M. dioica fruit extract are due to its antioxidant activity. It is further concluded that this antioxidant activity may be attributed to the phenolics, flavonoids and amino acids present in the extract.

Design and optimization of floating drug delivery system of acyclovir.

The purpose of the present work was to design and optimize floating drug delivery systems of acyclovir using psyllium husk and hydroxypropylmethylcellulose K4M as the polymers and sodium bicarbonate as a gas generating agent. The tablets were prepared by wet granulation method. A 3(2) full factorial design was used for optimization of drug release profile. The amount of psyllium husk (X1) and hydroxypropylmethylcellulose K4M (X2) were selected as independent variables. The times required for 50% (t(50%)) and 70% (t(70%)) drug dissolution were selected as dependent variables. All the designed nine batches of formulations were evaluated for hardness, friability, weight variation, drug content uniformity, swelling index, in vitro buoyancy, and in vitro drug release profile. All formulations had floating lag time below 3 min and constantly floated on dissolution medium for more than 24 h. Validity of the developed polynomial equation was verified by designing two check point formulations (C1 and C2). The closeness of predicted and observed values for t(50%) and t(70%) indicates validity of derived equations for the dependent variables. These studies indicated that the proper balance between psyllium husk and hydroxypropylmethylcellulose K4M can produce a drug dissolution profile similar to the predicted dissolution profile. The optimized formulations followed Higuchi's kinetics while the drug release mechanism was found to be anomalous type, controlled by diffusion through the swollen matrix.

Effect of Momordica dioica Roxb on gentamicin model of acute renal failure.

The ethanolic extract of the fruits of Momordica dioica was studied for its protective and curative effect against gentamicin-induced acute renal injury in albino rats of both sexes. Gentamicin intoxicated group showed significant increase in blood urea (69.48 +/- 4.34) and serum creatinine (3.017 +/- 0.208) from normal levels 33.72 +/- 1.92 and 0.818 +/- 0.073, respectively, in control group. In the preventive regimen, the extract at dose levels of 200 mg kg(-1) showed significant reduction in the elevated blood urea (47.93 +/- 2.46) and serum creatinine (2.067 +/- 0.1745), respectively. This treatment normalised the histopathological changes compared to the intoxicated group. In the curative regimen at 200 mg kg(-1) blood urea was found to be 48.21 +/- 2.36 and serum creatinine level was 2.050 +/- 0.183, which revealed significant curative effect. In vivo antioxidant and free radial scavenging activities were also determined. The maximum free radical scavenging activity with ethanolic extract was the basis of selection of this extract for in vivo study. Reduced glutathione (GSH) level was significantly (p < 0.05) increased in the extract treated groups whereas malondialdehyde (MDA) was reduced significantly (p < 0.05). High content of flavonoids and phenolic compounds was found in ethanolic extract, which may be responsible for free radical activity. The findings suggest that the ethanol extract of Momordica dioica seeds possesses marked nephroprotective and curative activities without any toxicity due to its antioxidant activity and could offer a promising role in the treatment of acute renal injury caused by nephrotoxin-like gentamicin.

Role of chelates in treatment of cancer.

Chelates are used in cancer as cytotoxic agent, as radioactive agent in imaging studies and in radioimmunotherapy. Various chelates based on ruthenium, copper, zinc organocobalt, gold, platinum, palladium, cobalt, nickel and iron are reported as cytotoxic agent. Monoclonal antibodies labeled with radioactive metals such as yttrium-90, indium-111 and iodine-131 are used in radioimmunotherapy. This review is an attempt to compile the use of chelates as cytotoxic drugs and in radioimmunotherapy.

Wound healing potential of Tephrosia purpurea (Linn.) Pers. in rats.

Tephrosia purpurea is a well-known herb for its hepatoprotective, anticancer, antiulcer, antibacterial and in healing bleeding piles, etc. The present study was aimed for wound healing potential of ethanolic extract of Tephrosia purpurea (aerial part) in the form of simple ointment using three types of wound models in rats as incision wound, excision wound and dead space wound. The results were comparable to standard drug Fluticasone propionate ointment, in terms of wound contraction, tensile strength, histopathological and biochemical parameters such as hydroxyproline content, protein level, etc. Histopathological study showed significant (P<0.05) increase in fibroblast cells, collagen fibres and blood vessels formation. All parameters were observed significant (P<0.05) in comparison to control group.

Antimicrobial activity of the roots of cocculus hirsutus.

Cocculus hirsutus Linn was studied for antimicrobial activity against Staphylococcus aureus, Echerchia coli, Pseudomonas aeruginosa and Salmonella typhi using agar disc-diffusion method. Petroleum ether extract, Ethanolic extract and Crude alkaloidal fraction were screened for the activity in various concentrations and zone of inhibitions were recorded. Results suggest that the Ethanolic extract and Crude alkaloidal fraction have significant antimicrobial activity against test microorganisms and the activity is found to be concentration dependent. Present findings justify the claimed uses of Cocculus hirsutus in the indigenous systems of medicine to treat various infectious diseases.

Analgesic activity of the roots of baliospormum montanum linn.

The ethanolic extract and its chloroform soluble and chloroform insoluble fractions of the roots of Baliospermum montanum were investigated in albino rats to evaluate the analgesic activity. Tailo - flick animal model was employed to test analgesic activity and compaired with a standard drug, Diclofenac sodium. The results indicate that the ethanolic extract and its chloroform soluble fraction are significantly effective (p<0.05) with respect to standard. The activity was found to be dose dependant. Results of present study justify the folklore use of B.montanum as analgesic drug.

Evaluation of an aqueous injection of ketoprofen.

The increase in aqueous solubility of ketoprofen using hydrotropes and cosolvents in formulation, as well as stability studies of its aqueous injections have been reported earlier. These formulations were further evaluated in vitro (physical evaluation, haemolytic activity) and in vivo (pharmacokinetic studies). Some of the formulations have shown promising results.

Cosolvent solubilization and formulation of an aqueous injection of ketoprofen.

Ketoprofen (1) an analgesic, antipyretic and anti-inflammatory agent, is practically insoluble in water. An increase in the aqueous solubility of 1 was attempted by various cosolvents. The solubility increased up to 8556 times (maximum) in case of ethanol while it was 33 times (minimum) in case of glycerol. Using selected cosolvents and hydrotropes, aqueous injections of 1 were formulated.