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Dolastatin 10 (Dol-10), a natural marine-source pentapeptide, is a powerful antimitotic agent regarded as one of the most potent anticancer compounds found to date. Dol-10 however, lacks chemical conjugation capabilities, which restricts the feasibility of its application in targeted drug therapy. This limitation has spurred the prospect that chemical structure of the parent molecule might allow conjugation of the derivatives to drug carriers such as antibodies. By first employing docking studies, we designed and prepared a series of novel Dol-10 analogs with a modified C-terminus, preserving high potency of the parent compound while enhancing conjugation capability. The modifications involved the introduction of a methyleneamine functionality at position 4 of the 1,3-thiazole ring, along with the substitution of the thiazole ring with a 1,2,3-triazole moiety, furnished with methylenehydroxy, carboxy, methyleneamine, and N(Me)-methyleneamine tethering functionalities at position 4. Among the synthesized pentapeptides, DA-1 exhibited the highest potency in prostate cancer (PC-3) cells, eliciting apoptosis (IC50 0.2 ± 0.1 nm) and cell cycle arrest at the mitotic stage after at least 6 days of culture. This delayed response suggests the accumulation of cellular stress or significant physiological alterations that profoundly impact the cell cycle. We believe that these novel Dol-10 derivates represent a new and straightforward route for the development of C-terminus modified Dol-10-based microtubule inhibitors, thereby advancing targeted anticancer therapy.
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Antineoplásicos , Proliferación Celular , Depsipéptidos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Relación Estructura-Actividad , Depsipéptidos/química , Depsipéptidos/farmacología , Depsipéptidos/síntesis química , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Estructura Molecular , Relación Dosis-Respuesta a Droga , Simulación del Acoplamiento Molecular , Apoptosis/efectos de los fármacos , Compuestos Heterocíclicos/química , Compuestos Heterocíclicos/farmacología , Compuestos Heterocíclicos/síntesis químicaRESUMEN
Background: Effective postoperative analgesia after lower segment caesarean section (LSCS) is very important for early ambulation and early breast feeding and has a role to play in decreasing postpartum depression. Quadratus lumborum (QL) block, a fascial plane block, is gaining popularity for pain management in lower abdominal surgeries. The aim of the present study was to compare the ultrasound-guided (USG) transversus abdominis plane (TAP) block and QL block in patients undergoing LSCS under spinal anaesthesia. Methods: Double-blinded, randomized, controlled, single-centre study done between Aug 2019 and Oct 2019, randomised 80 patients scheduled for LSCS into two groups, QL (N = 40) and TAP (N = 40), receiving USG TAP or QL block 20 ml of 0.25% bupivacaine with 4 mg dexamethasone bilaterally, postoperatively. Results: SSPS 20 was used for the statistical analysis Patients were evaluated for 24-h using visual analogue scale (VAS) for pain scores, time to rescue analgesia and the analgesic dose requirement at regular time intervals. Fifteen percent patients in QL block and 75% in TAP block required rescue analgesia (P < 0.001). Significant differences were observed in pain scores at 10 h postoperatively, VAS in QL=1.18 (0.55), TAP=3.08 (1.66) (P < 0.001). By 24 h postoperatively the difference ceased to be statistically significant. Time to rescue analgesia in QL group was 1353 min (+/-224.07) and TAP group 915 min (+/-391.62) (P < 0.001). Average requirement of rescue analgesia (paracetamol) in QL group was 153.84 mg, TAP group 756.09 mg. Conclusions: Patients receiving QL block had prolonged analgesic effects and required less use of rescue analgesia in comparison with TAP group in the first 24 h postoperatively. Trial number: CTRI/2019/07/020475.
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COVID-19, a pandemic of the 21st century caused by novel coronavirus SARS-CoV-2 was originated from China and shallowed world economy and human resource. The medical cures via herbal treatments, antiviral drugs, and vaccines still in progress, and studying rigorously. SARS-CoV-2 is more virulent than its ancestors due to evolution in the spike protein(s), mediates viral attachment to the host's membranes. The SARS-CoV-2 receptor-binding spike domain associates itself with human angiotensin-converting enzyme 2 (ACE-2) receptors. It causes respiratory ailments with irregularities in the hepatic, nervous, and gastrointestinal systems, as reported in humans suffering from COVID-19 and reviewed in the present article. There are several approaches, have been put forward by many countries under the world health organization (WHO) recommendations and some trial drugs were introduced for possible treatment of COVID-19, such as Lopinavir or Ritonavir, Arbidol, Chloroquine (CQ), Hydroxychloroquine (HCQ) and most important Remdesivir including other like Tocilizumab, Oritavancin, Chlorpromazine, Azithromycin, Baricitinib, etc. RT-PCR is the only and early detection test available besides the rapid test kit (serodiagnosis) used by a few countries due to unreasonable causes. Development of vaccine by several leader of pharmaceutical groups still under trial or waiting for approval for mass inoculation. Management strategies have been evolved by the recommendations of WHO, specifically important to control COVID-19 situations, in the pandemic era. This review will provide a comprehensive collection of studies to support future research and enhancement in our wisdom to combat COVID-19 pandemic and to serve humanity.
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Type 2 diabetes mellitus (T2DM) accounts for >90% of the cases of diabetes in adults. Resistance to insulin action is the major cause that leads to chronic hyperglycemia in diabetic patients. T2DM is the consequence of activation of multiple pathways and factors involved in insulin resistance and ß-cell dysfunction. Also, the etiology of T2DM involves the complex interplay between genetics and environmental factors. This interplay can be governed efficiently by lifestyle modifications to achieve better management of diabetes. The present review aims at discussing the major factors involved in the development of T2DM that remain unfocussed during the anti-diabetic therapy. The review also focuses on lifestyle modifications that are warranted for the successful management of T2DM. In addition, it attempts to explain flaws in current strategies to combat diabetes. The employability of phytoconstituents as multitargeting molecules and their potential use as effective therapeutic adjuvants to first line hypoglycemic agents to prevent side effects caused by the synthetic drugs are also discussed.
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Diabetes Mellitus Tipo 2/fisiopatología , Diabetes Mellitus Tipo 2/terapia , Estilo de Vida Saludable , Tejido Adiposo/metabolismo , Glucemia , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/genética , Dieta , Suplementos Dietéticos , Quimioterapia Combinada , Ejercicio Físico , Microbioma Gastrointestinal/fisiología , Humanos , Hipoglucemiantes/uso terapéutico , Polipéptido Amiloide de los Islotes Pancreáticos/metabolismo , Islotes Pancreáticos/metabolismo , Fitoterapia/métodos , Resistina/metabolismo , SueñoRESUMEN
The type 2 diabetes is one of the major global health issues that affects millions of people. This study evaluated the antidiabetic activity of aqueous extracts (AECP) and methanol extracts (MECP) from Ceiba pentandra trunk bark on an experimental model of type 2 diabetes (T2D). This model was induced in rats by the combination of a high-fat diet (HFD) and a single dose of streptozotocin (40 mg/kg, intraperitoneal) at the seventh day of experimentation. Diabetes was confirmed on day 10 by fasting blood glucose more than or equal to 200 mg/dL. Diabetic animals still under HFD were treated orally and twice daily, with MECP and AECP (75 and 150 mg/kg) or metformin (40 mg/kg) for 14 days. During the experiment, blood glucose and animal weights were determined. Oral glucose tolerance test was performed on day 15, followed by animals sacrifice for blood, liver, and pancreas collection. Total cholesterol and triglyceride levels were evaluated in plasma, whereas malondialdehyde (MDA), glutathione (GSH), superoxide dismutase, and catalase were quantified in tissue homogenates. AECP and MECP significantly reduced the hyperglycemia by up to 62% and significantly improved the oral glucose tolerance test. The impaired levels of cholesterol and triglycerides registered in diabetic control were significantly reversed by both extracts at all the doses used. Alterations in diabetic pancreas weight, GSH, and MDA were also significantly reversed by plant extracts. AECP and MECP possess type 2 antidiabetic effects that could result from their ability to improve the peripheral use of glucose, lipid metabolism or from their capacity to reduce oxidative stress. These finding provide a new avenue for better control and management of early or advanced T2D.
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BACKGROUND: Hydrogen sulphide (H2S), a member of the gasotransmitters family, is known to play patho-physiological role in different body systems including during pregnancy. But its involvement in myometrial spontaneity and associated signalling pathways in uterus in non-pregnant animals is yet to be studied. Present study describes the effect of L-cysteine, an endogenous H2S donor, on isolated myometrial strips of non-pregnant buffaloes and the underlying signaling mechanism(s). RESULTS: L-cysteine (10 nM-30 mM) produced concentration-dependent contractile effect on buffalo myometrium which was extracellular Ca2+ and L-type calcium channels-dependent. Significant rightward shift of dose-response curve of L-cysteine was observed with significant decrease in maxima in the presence of amino-oxyacetic acid (AOAA; 100 µM) and d, l-propargylglycine (PAG; 100 µM), the specific blockers of cystathionine ß-synthase (CBS) and cystathionine γ-lyase (CSE), respectively. Existence of CBS enzyme of 63 kDa and CSE of 45 kDa molecular weights was confirmed by western blot using specific antibodies and also by immunohistochemistry. CONCLUSIONS: Endogenous H2S along with its biosynthetic enzymes (CBS and CSE) is evidently present in uteri of non-pregnant buffaloes and it regulates spontaneity in uteri of non-pregnant buffaloes and this effect is dependent on extracellular Ca2+ influx through nifedipine-sensitive L-type calcium channels. Thus H2S-signalling pathway may be a potential target to alter the uterine activities in physiology and patho-physiolgical states.
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Búfalos/fisiología , Sulfuro de Hidrógeno/metabolismo , Miometrio/fisiología , Alquinos/farmacología , Ácido Aminooxiacético/farmacología , Animales , Western Blotting/veterinaria , Búfalos/metabolismo , Cisteína/farmacología , Relación Dosis-Respuesta a Droga , Femenino , Glicina/análogos & derivados , Glicina/farmacología , Miometrio/efectos de los fármacos , Miometrio/metabolismoRESUMEN
Liposomes are well known lipid carriers for drug delivery of bioactive molecules encapsulated inside their membrane. Liposomes as skin drug delivery systems were initially promoted primarily for localized effects with minimal systemic delivery. Subsequently, a novel vesicular system, transferosomes was reported for transdermal delivery with efficiency similar to subcutaneous injection. The multiple bilayered organizations of lipids applied in these vesicles structure are somewhat similar to complex nature of stratum corneal intercellular lipids domains. The incorporation of novel agents into these lipid vesicles results in the loss of entrapped markers but it is similar to fluidization of stratum corneum lipids on treatment with a penetration enhancer. This approach generated the utility of penetration enhancers/fluidizing agents in lipids vesicular systems for skin delivery. For the transdermal and topical applications of liposomes, fluidity of bilayer lipid membrane is rate limiting which governs the permeation. This article critically reviews the relevance of using different types of vesicles as a model for skin in permeation enhancement studies. This study has also been designed to encompass all enhancement measurements and analytical tools for characterization of permeability in liposomal vesicular system.
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Liposomas/química , Fluidez de la Membrana , Administración Cutánea , Animales , Rastreo Diferencial de Calorimetría , Difusión , Sistemas de Liberación de Medicamentos , Elasticidad , Espectroscopía de Resonancia por Spin del Electrón , Epidermis , Fluidez de la Membrana/efectos de los fármacos , Ratones Pelados , Permeabilidad , Fosfatidilcolinas/química , Absorción Cutánea , Tensoactivos/química , TermodinámicaRESUMEN
Isabgol husk, a medicinally important natural polysaccharide was applied for fabrication of hydrogel beads by ionic gelation method to incorporate gliclazide. Different strengths of Isabgol husk and sodium alginate were utilized for assessing the process variables on formulation performance. Aqueous solution of calcium chloride in 2, 5 and 8% w/v strength was used as cross-linker for polymeric blends of Isabgol husk and sodium alginate. The formulations were characterized for various parameters such as particle size, swelling index, entrapment efficiency, in vitro release, and release kinetics. The quantification of gliclazide throughout the study was performed by HPLC method which was validated according to ICH guidelines for system suitability, linearity, accuracy, sensitivity, precession, robustness, and ruggedness. The surface morphology of beads was observed by scanning electron microscopy. The formed beads were brown, free flowing, spherical, and irregular in structure. The size in different formulations varied from 752.83 +/- 0.630 to 838.62 +/- 0.741 microm. The beads remained for 2-3 h in alkaline phosphate buffer (pH 7.4), after that they showed disintegration. The formulations released up to 95% of loaded gliclazide in phosphate buffer (pH 7.4) within 8 h. No significant difference was observed in parameters studied such as particle size, entrapment efficiency and swelling index for hydrogel beads during accelerated stability study (p > 0.05). The regression equation developed by HPLC method was linear (r5 > 0.9990) over the range 2.5 to 10 microg/mL. The limit of detection (LOD) and limit of quantification (LOQ) were 0.037619 microg/mL and 0.113997 microg/mL, respectively. The observed values for number of theoretical plates (N > or = 2000), tailing factor (T < or = 2), asymmetry factor (AF < or = 1), and relative standard deviation (RSD < or = 1%) of applied method showed the reliability for gliclazide estimation in Isabgol husk hydrogel beads.
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Cromatografía Líquida de Alta Presión/métodos , Gliclazida/química , Psyllium , Química Farmacéutica , Estabilidad de Medicamentos , Hidrogeles/química , Tamaño de la Partícula , SolubilidadRESUMEN
Background: Anterior cervical discectomy and fusion (ACDF) is one of the most frequently performed cervical surgeries in the world, yet there have been several reported complications. Objective: To determine the actual incidence of complications related to ACDF as well as any risk variables that may have been identified in earlier research. Methods: To evaluate the origin, presentation, natural history, and management of the risks and the complications, we conducted a thorough assessment of the pertinent literature. An evaluation of clinical trials and case studies of patients who experienced one or more complications following ACDF surgery was done using a PubMed, Cochrane Library, and Google Scholar search. Studies involving adult human subjects that were written in the English language and published between 2012 and 2022 were included in the search. The search yielded 79 studies meeting our criteria. Results: The overall rates of complications were as follows: Dysphagia 7.9%, psudarthrosis 5.8%, adjacent segment disease (ASD) 8.8%, esophageal perforations (EPs) 0.5%, graft or hardware failure 2.2%, infection 0.3%, recurrent laryngeal nerve palsy 1.7%, cerebrospinal fluid leak 0.8%, Horner syndrome 0.5%, hematoma 0.8%, and C5 palsy 1.9%. Conclusion: Results showed that dysphagia was a common postoperative sequelae with bone morphogenetic protein use and a higher number of surgical levels being the major risk factors. Pseudarthrosis rates varied depending on the factors such as asymptomatic radiographic graft sinking, neck pain, or radiculopathy necessitating revision surgery. The incidence of ASD indicated no data to support anterior cervical plating as more effective than standalone ACDF. EP was rare but frequently fatal, with no correlation found between patient age, sex, body mass index, operation time, or number of levels.
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Background: Tennis elbow (lateral epicondylitis elbow) is a self-limiting disease of indeterminate pathogenesis. Conservative therapy is the treatment of choice. In chronic tennis elbow with failure of conservative therapy; surgical treatment is a method of choice. Percutaneous tenotomy of extensor origin for patients with chronic tennis elbow is a minimally invasive technique with better long-term outcomes. Case Report: Ten patients (six males, four females) presented with chronic tennis elbow, who did not respond to conservative treatment/non-surgical intervention for more than 6 months underwent percutaneous tenotomy in an outpatient setting. Two patients were lost to follow-up at 2 months' post-operative. The remaining eight patients were evaluated at a mean follow-up of 3 years and assessed using the numerical rating scale, disabilities of the arm, shoulder and hand questionnaire ,and Oxford elbow score. These scores had a statistically significant difference in baseline to 3-year follow-up values (P < 0.05). No adverse outcomes, recurrence of symptoms, and signs of lateral epicondylitis elbow were noted and none required open surgical release. Conclusion: Percutaneous tenotomy, a minimally invasive technique is an effective and well-tolerated treatment for chronic tennis elbow and gives good pain relief and functional recovery.
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Introduction: Gap non-union patellas are challenging to treat for an orthopedic surgeon. We hereby report a case of a 22-year-old person with a 3 cm gap nonunion, its surgical management, functional outcome, and implications for clinical practice. Case Report: A 22-year-old active male presented to us with a background of comminuted fracture patella left side that he suffered 1 year ago, following which he was treated by open reduction and internal fixation (ORIF) with Tension Band Wiring (TBW). One year post-surgery, the patient had another fall, following which he had pain swelling in his left knee and difficulty in his knee extension. The patient presented 6 months later with painful ambulation and a swelling left knee. A 3 cm gap along with underlying implants could be palpated. The patient underwent surgery in the form of previous implant removal, freshening and apposition of fracture ends, and single-staged reconstruction of the extensor mechanism using TBW. The patient had full range of motion at the 1-year follow-up. Conclusion: The present case highlights the fact that small-gap non-union patella can be managed simply as a single-stage procedure with ORIF and TBW.
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The current study focuses on examining the characteristics of biofuel obtained from the pyrolysis of Madhuca longifolia residues, since the selected forest residue was primarily motivated by its greater volatile matter content. The study used several analytical techniques to describe pyrolysis oil, char, and gas obtained from slow pyrolysis process conducted between 350 and 600 °C in a fixed-bed reactor. Initially, the effect of process temperature on product distribution was assessed to motivate maximum pyrolysis oil yield and found to be 44.2 wt% at pyrolysis temperature of 475 °C, while the yields of char and gas were 22.1 wt% and 33.7 wt%, respectively. In order to determine the suitability of the feedstock, the Madhuca longifolia residues were analyzed by TGA and FT-IR, which revealed that the feedstock could be a feasible option as an energy source. The characterization of pyrolysis oil, char, and gas has been done through various analytical methods like FT-IR, GC-MS, and gas chromatography. The physicochemical characteristics of the pyrolysis oil sample were examined, and the results showed that the oil is a viscous liquid with a lower heating value than conventional diesel. The FT-IR and GC-MS analysis of pyrolysis oil revealed the presence of increased levels of oxygenated chemicals, acids, and phenol derivatives. The findings of the FT-IR analysis of char indicated the existence of aromatic and aliphatic hydrocarbons. The increased carbon content in the char indicated the possibility of using solid fuel. Gas chromatography was used to examine the chemical structure of the pyrolysis gas, and the results showed the existence of combustible elements.
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Biocombustibles , Cromatografía de Gases y Espectrometría de Masas , Madhuca , Pirólisis , Biocombustibles/análisis , Espectroscopía Infrarroja por Transformada de Fourier , Madhuca/química , Termogravimetría , CalorRESUMEN
Swasthya Rakshan Programme (SRP) provides health care services through Ayurveda, an initiative of the Government of India that aims to survey and create alertness of essential health appliances to ameliorate society from its grassroots level. The present study aimed to survey the prevailing health standards of residents in certain districts of India and to record the prevalence of diseases among them according to their living conditions, food habits, lifestyle, education, occupation and other socio-economic status. Data was collected through a community-based cross-sectional survey conducted from April 2018 to March 2019 in 22 Districts of 19 states in India. A stratified multi-stage sampling design was adopted for the survey. Documentation of demographic profile, food habits, lifestyle, hygiene status, and existing health conditions was assessed. A pre-designed semi-structured questionnaire was used for the collection of the data. Before initiating the programme, written consent was obtained. In this study, from 162 selected villages/colonies/areas, a total of 562,913 population and 81,651 households were surveyed. Sixty-nine thousand three hundred nineteen patients were cared for various ailments through health camps. The study found that the most prevalent disease in the concerned population was 'Sandhivata' (Osteo-arthritis), that is, 43.0%, followed by 'Dourbalya' (Debility), that is, 11.7%. The study includes insightful analyses of comprehensive demographic and health indicators classified by various socio-economic categories. The collected data regarding the prevalence of diseases with their sociodemographic correlations may provide a better understanding of the locality and thus may help in all future health endeavours.
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Non-alcoholic fatty liver disease (NAFLD) is an emerging global health problem and a potential risk factor for metabolic diseases. The bidirectional interactions between liver and gut made dysbiotic gut microbiome one of the key risk factors for NAFLD. In this study, we reported an increased abundance of Collinsella aerofaciens in the gut of obese and NASH patients living in India. We isolated C. aerofaciens from the fecal samples of biopsy-proven NASH patients and observed that their genome is enriched with carbohydrate metabolism, fatty acid biosynthesis, and pro-inflammatory functions and have the potency to increase ethanol level in blood. An animal study indicated that mice supplemented with C. aerofaciens had increased levels of circulatory ethanol, high levels of hepatic hydroxyproline, triglyceride, and inflammation in the liver. The present findings indicate that perturbation in the gut microbiome composition is a key risk factor for NAFLD.
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Tuberculosis is predicted to be a major undocumented cause of mortality in children. This systematic review with meta-analysis assessed the diagnostic accuracy of Lipoarabinomannan antigen testing (FujiLAM) in urine in HIV-negative children with TB-like signs and symptoms. PubMed, EMBASE, Scopus, Cochrane database and Google Scholar search engine were searched to identify relevant studies from earliest records to June 2022 without any language restriction. Three studies were finalized, patients were recruited from Africa and Haiti. Among microbiologically confirmed pediatric TB patients, pooled sensitivity and specificity of FujiLAM (with 95% CI) was 52% (35%-69%) and 90% (85%-93%) respectively. In both clinical (unconfirmed) and microbiological confirmed TB cases, sensitivity reduced to 24% (16%-34%) while specificity was 91%(80%-97%). We concluded that due to ease in obtaining urine sample, FujiLAM can be used as point-of-care TB test in HIV negative children, however more data from different population is needed.
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Infecciones por VIH , Mycobacterium tuberculosis , Tuberculosis , Humanos , Niño , Sistemas de Atención de Punto , Tuberculosis/diagnóstico , Tuberculosis/epidemiología , Lipopolisacáridos , Sensibilidad y Especificidad , Infecciones por VIH/diagnóstico , Pruebas Diagnósticas de RutinaRESUMEN
Introduction: Bilateral radial head fractures are a unique and rare presentation. Few studies are available in the literature documenting these type of injuries. We present a rare case of bilateral radial head fractures (Mason type 1) and managed conservatively with full functional recovery. Case Report: A 20-year-old male sustained bilateral radial head fractures (Mason type 1) following a roadside accident. The patient was managed conservatively with above elbow slab for 2 weeks followed by range of motion exercises. The patient had uneventful follow-up with full range of motion at elbow. Conclusion: Bilateral radial head fractures in a patient are a discreet clinical entity. A high index of suspicion, meticulous history, clinical examination, and appropriate imaging is essential in patients with history of fall on outstretched hands to avoid missing diagnosis. Early diagnosis, proper management, and appropriate physical rehabilitation lead to complete functional recovery.
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Objective: Incidences of post-transurethral resection of the prostate (post-TURP) strictures are between 2.2% and 9.8%. Stricture commonly occurs within the first 6 months. Our objective was to assess the outcomes of patients with obliterative strictures post-TURP that underwent a double-face urethroplasty. Methods: This is a single-center prospective study of 17 patients with obliterative proximal bulbar stricture post-TURP who underwent double-face graft urethroplasty by two surgeons between January 2014 and January 2020. We defined post-TURP obliterative strictures as those patients who presented with complete or almost complete obstruction of the urethral lumen and who have had a history of acute urine retention. We have excluded patients with bladder neck contracture. Primary outcome was treatment success, defined as the no need for further treatments. Secondary outcome was post-urethroplasty continent rate. Results: Seventeen patients were included in the study with median age of 66 (interquartile range 40-77) years; median time of follow-up was 24 (interquartile range 12-84) months; median stricture length was 4 (interquartile range 2-6) cm. Of the 17 patients, 15 (88.2%) were successful. All patients were continent after urethroplasty. Conclusion: With mid-term follow-up, treatment of obliterative proximal bulbar strictures with double-face buccal mucosa graft is a safe and effective procedure. Obliterative proximal bulbar strictures merit double-face urethroplasty with high-rate success and functional outcomes.
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We evaluated the effects of select herbal extracts (Tinospora cordifolia [TC], Tinospora cordifolia with Piper longum [TC + PL], Withania somnifera [WS], Glycyrrhiza glabra [GG], AYUSH-64 [AY-64], and Saroglitazar [S]) on various parameters in a diet-induced obesity mouse model. After 12 weeks of oral administration of the herbal extracts in high-fat diet (HFD)-fed C57BL/6J mice, we analyzed plasma biochemical parameters, insulin resistance (IR), liver histology, and the expression of inflammatory and fibrosis markers, along with hepatic lipidome. We also used a 3D hepatic spheroid model to assess their impact on profibrotic gene expression. Among the extracts, TC + PL showed a significant reduction in IR, liver weight, TNF-α, IL4, IL10 expression, and hepatic lipid levels (saturated triglycerides, ceramides, lysophosphocholines, acylcarnitines, diglycerides, and phosphatidylinositol levels). Saroglitazar reversed changes in body weight, IR, plasma triglycerides, glucose, insulin, and various hepatic lipid species (fatty acids, phospholipids, glycerophospholipids, sphingolipids, and triglycerides). With the exception of GG, Saroglitazar, and other extracts protected against palmitic acid-induced fibrosis marker gene expression in the 3D spheroids. TC + PL and Saroglitazar also effectively prevented HFD-induced insulin resistance, inflammation, and specific harmful lipid species in the liver.
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Enteral alimentation can be administered continuously, cyclically, intermittently, or by a bolus technique. Current literature does not suggest superiority of any one regime. Most studies have used nasogastric feeds, little is known about the outcome of jejunal feeding.This study compares the efficiency and safety of bolus and continuous jejunostomy feeding. 46 adults undergoing a feeding jejunostomy for nutritional support or as an adjunct to a major upper GI surgery, were randomised to bolus feeding (BF group, n = 24) and continuous feeding (CF group, n = 22). Demographic, anthropometric, and laboratory parameters were measured preoperatively and on post-operative days (POD) 3, 7, 15, and 30. These parameters; as well as nutritional and functional outcomes, and complications at POD 30; were comparable in both groups. Both groups tolerated jejunal feeds well. Bolus feeding is simple, inexpensive, and permits daily physical activities. Hence it may be preferred over continuous jejunostomy feeding for enteral alimentation.