Impact of alogliptin on lipopolysaccharide-induced experimental Parkinson's disease: Unrevealing neurochemical and histopathological alterations in rodents.

BACKGROUND: Degeneration of the nigrostriatal dopaminergic pathway has been seen as a significant cause of movement disability in Parkinson's disease (PD) patients. However, the exact reason for these degenerative changes has remained obscure. In recent years, incretins have been neuroprotective in various pathologies. In the current study, we have investigated the neuroprotective potential of alogliptin (Alo), a dipeptidyl peptidase-IV (DPP-IV) inhibitor, in a lipopolysaccharide (LPS) induced experimental model of PD. EXPERIMENTAL APPROACH: LPS (5µg/5 µl) was infused intranigrally to induce PD in experimental rats. Post-LPS infusion, these animals were treated with Alo for 21 days in three successive dosages of 10, 20, and 40 mg/kg/day/per oral. The study is well supported with the determinations of motor functions biochemical, neurochemical, and histological analysis. KEY RESULTS: Intranigral infusion of LPS in rats produced motor deficit. It was accompanied by oxidative stress, elevation in neuroinflammatory cytokines, altered neurochemistry, and degenerative changes in the striatal brain region. While Alo abrogated LPS-induced biochemical/neurochemical alterations, improved motor functions, and preserved neuronal morphology in LPS-infused rats. CONCLUSION: The observed neuroprotective potential of Alo may be due to its antioxidant and anti-inflammatory actions and its ability to modulate monoaminergic signals. Nonetheless, current findings suggest that improving the availability of incretins through DPP-IV inhibition is a promising strategy for treating Parkinson's disease.

A comparative study of uncomplicated acute non-A-E hepatitis with acute viral hepatitis and acute onset autoimmune hepatitis.

BACKGROUND AND AIMS: Non-A-E hepatitis (NAEH) not leading to acute liver failure (ALF) is poorly documented. The objective was to compare clinical and laboratory features of uncomplicated acute NAEH with acute viral (AVH) and autoimmune hepatitis (AIH) and histopathology in NAEH and AIH. METHODS: Cases of hepatocellular jaundice were included. These were grouped into AVH, AIH and NAEH based on clinical, laboratory and, when indicated, liver biopsy findings. NAEH and AIH were followed up at three months. RESULTS: Of 336 patients with hepatocellular jaundice, 15 (5%) were NAEH, 25 (7%) acute AIH and 45 (14%) AVH. Among NAEH patients, seven (46.7%) were males with a mean age of presentation 39 years. Jaundice (100%) was the most common presentation of NAEH. Peak bilirubin was 10.7 mg/dL. Peak aspartate and alanine aminotransferase (AST, ALT) were 512 and 670 U/L. Five (33.3%) patients had positive anti-nuclear antibody and one had anti-smooth muscle antibody. Mean immunoglobulin G (IgG) levels were 1829. On liver biopsy, all had ballooning degeneration, four (26.7%) had mild and three (20%) moderate interface hepatitis, four (26.7%) mild lymphoplasmacytic infiltrate, one (6.7%) rosette formation, bridging necrosis in none and stage 1 fibrosis in one. Comparing NAEH with AIH, AIH showed significantly older age at presentation, female predisposition, past history of jaundice, lower ALT, more autoantibodies, higher IgG, higher grade interface hepatitis, lymphoplasmacytic infiltrate, rosette formation and higher bilirubin, AST at three months. NAEH and viral hepatitis had similar features. CONCLUSION: Etiology of NAEH is unlikely to be autoimmune and is probably viral, unidentified as yet. Uncomplicated NAEH likely has self-limiting course even without specific treatment.

Dipeptidyl peptidase 4(DPP4) inhibitors stride up the management of Parkinson's disease.

Parkinson's disease (PD) is the 2nd most common age-related hypokinetic disorder, characterized by dopaminergic degeneration and movement abnormalities. Dopaminergic degeneration in the basal ganglia is primarily seen in PD patients. The therapeutic strategies currently under investigation are to rescue dopaminergic degeneration and promote neuronal regeneration, which could halt disease progression. On the other hand, the therapeutic efficacy of existing drugs used in other disorders has been repurposed in neurodegenerative pathologies. DPP4 inhibitors widely used in treating diabetes have been considered viable target sites and are being tested for efficacy in neurodegenerative pathologies. DPP4 inhibitors have been reported to rescue neuronal degeneration and improve motor functions in various preclinical and clinical PD studies. The current review is focused on the neuroprotective potential, molecular mechanisms and therapeutic potential of DPP4 inhibitors in PD pathology.

Vinpocetine restores cognitive and motor functions in Traumatic brain injury challenged rats.

Traumatic brain damage is common worldwide and the treatments are not well-defined. Vinpocetine is a synthetic derivative of the vinca alkaloid vincamine and is clinically being used for various brain disorders. Here in the current study, we have investigated the neuroprotective potential of vinpocetine against traumatic brain injury. TBI was induced by the Marmarou weight drop method in rats. Brain damage was evaluated using cognitive and motor functions and the alterations in biomolecules. Injured rats were treated with different doses of vinpocetine (2.5, 5, and 10 mg/kg) for 4 weeks. Traumatic brain injury in rats produced significant deterioration of cognition and motor functions, which was accompanied by increased oxidative stress and significant alterations in brain monoamine levels as compared with the sham control group (p < 0.05). Vinpocetine alleviated TBI-induced oxidative burden, altered neurochemistry, and improved the cognitive and motor functions as compared with that of the TBI control group (p < 0.05). The observed neuroprotective potential of vinpocetine may be due to the observed antioxidant potential and its ability to restore the levels of brain neurochemicals under stressed conditions. The outcomes of the current study may help the repositioning of vinpocetine for preventing or treating traumatic brain injuries.

Normal Values of High-resolution Anorectal Manometry of Healthy Indians.

Background/Aims: High-resolution anorectal manometry (HRAM) measures anal sphincter function and anorectal co-ordination. This study aims to provide normal data for HRAM and evaluate the effect of gender, age, and body mass index (BMI) on anorectal functions in healthy Indian subjects. Methods: HRAM was performed on 93 healthy volunteers using a 20-channel, water-perfused catheter. We evaluated anorectal pressures, rectal sensation, and balloon expulsion time. Measurements were recorded during rest, squeeze, and simulated defecation (push). Results: Median anal resting pressure (88 mmHg vs 94 mmHg, P = NS), anal squeeze pressure (165 mmHg vs 147 mmHg, P = NS) were not significantly different between males and females. Rectal pressure (70 mmHg vs 54 mmHg, P = 0.024) and anal pressure (82 mmHg vs 63 mmHg, P = 0.008) during simulated evacuation without rectal distention, were higher in males. The threshold for the first sensation was lower in females (40 mL vs 30 mL, P = 0.021) but desire to defecate (105 mL vs 90 mL, P = NS) and maximum tolerable volume (160 mL vs 140 mL, P = NS) were not significantly different in males and females. Anal residual pressure (median mmHg 83 vs 71 mmHg, P = 0.025) was higher in subjects < 40 years of age. Maximum anal squeeze pressure (185 mmHg vs 165 mmHg, P = 0.024) and maximum rectal pressure (75 mmHg vs 62 mmHg, P = 0.032) during push higher in BMI < 23 kg/m2. Conclusions: The present study provides normal data for the Indian population that can be used for comparison and further work. Age, gender, and BMI affect anorectal parameters in HRAM and should be considered while reporting.

Artificial Intelligence in Medicine.

Artificial intelligence as the name suggests is intelligence given to machines by man. AI learns and performs like humans without human instructions. We encounter AI in daily activities, like music and video suggestions in video applications, and personalize what we see on Facebook, Twitter, Instagram. AI makes our day-to-day life easier, efficient and it increases the speed and accuracy of our efforts. In this article, we reviewed previous articles and internet sites to understand the general principles of artificial intelligence. We included general articles and few articles related to medicine to understand the basics of AI and its application in the medical field. A literature search was done using the following search terms: 'AI' and 'AI in medicine'.

A review: traditional herbs and remedies impacting pathogenesis of Parkinson's disease.

Parkinson's disease (PD) is characterized by progressive degeneration of dopaminergic neurons, leading to misbalance and loss of coordination. Current therapies are claimed only for symptomatic relief, on long-term use, which causes alteration in basal ganglia, and give rise to various adverse effects like dyskinesia and extra pyramidal side effects, which is reversed and proved to be attenuated with the help of various herbal approaches. Therefore, in order to attenuate the dopaminergic complications, focus of current research has been shifted from dopaminergic to non-dopaminergic strategies. Herbs and herbal remedies seems to be a better option to overcome the complications associated with current dopaminergic therapies. In recent years, various herbs and herbal remedies based on Ayurveda, traditional Chinese and Korean remedies, have become the target of various researches. These herbs and their bioactive compound are being extensively used to treat PD in India, China, Japan, and Korea. The major focus of this current review is to analyze preclinical studies with reference to various herbs, bioactive compounds, and traditional remedies for the management of Parkinson disorder, which will give an insight towards clinical trials.

Predictors of Severity and Mortality in Chronic Liver Disease Patients With COVID-19 During the Second Wave of the Pandemic in India.

Background Coronavirus disease 2019 (COVID-19) infection in chronic liver disease patients is associated with poor outcomes. In this study, we aimed to evaluate the predictors of severity and mortality in this group of patients during the second wave of the COVID-19 pandemic in India. In addition, we compared cirrhotic patients with COVID-19 with cirrhotic patients from the pre-COVID-19 period. Methodology This was a single-center observational study. We included data from 50 patients with cirrhosis and COVID-19 retrospectively from the discharge/death files. A comparison group of 100 patients with cirrhosis from the pre-COVID period was also analyzed retrospectively. Results The majority of patients had predominantly respiratory symptoms, with fever being the most common symptom (85%). The most common presentation was acute on chronic liver failure (ACLF). The most common form of decompensation was jaundice followed by hepatic encephalopathy. The overall mortality in cirrhotic patients with COVID-19 was double than that in cirrhotic patients from the pre-COVID-19 period. All patients with ACLF succumbed to multiorgan failure. Diabetes was the only comorbidity that was associated with severe infection. Higher creatinine on admission and high D-dimer levels correlated with severity. D-dimer was the only parameter that correlated with severity and mortality on multivariate analysis. None of the comorbidities predicted mortality. Among various composite scores, the Child-Turcotte-Pugh (CTP) score and CURB-65 correlated with mortality. On the area under the receiver operating characteristic analysis, a D-dimer level of >1.1 mg/L was associated with mortality. Conclusions COVID-19 infection in patients with cirrhosis is associated with poor outcomes. D-dimer levels of >1.1 mg/L on admission are a simple parameter to predict mortality. CTP and CURB-65 are composite scores that correlate with mortality in this group of patients.

Orienting an Organic Semiconductor into DNA 3D Arrays by Covalent Bonds.

A quasi-one-dimensional organic semiconductor, hepta(p-phenylene vinylene) (HPV), was incorporated into a DNA tensegrity triangle motif using a covalent strategy. 3D arrays were self-assembled from an HPV-DNA pseudo-rhombohedron edge by rational design and characterized by X-ray diffraction. Templated by the DNA motif, HPV molecules exist as single-molecule fluorescence emitters at the concentration of 8 mM within the crystal lattice. The anisotropic fluorescence emission from HPV-DNA crystals indicates HPV molecules are well aligned in the macroscopic 3D DNA lattices. Sophisticated nanodevices and functional materials constructed from DNA can be developed from this strategy by addressing functional components with molecular accuracy.

Pattern of liver function test variations in COVID-19 infection & its clinical significance: A study from a dedicated COVID-19 tertiary care centre from India.

Background & objectives: Coronavirus disease 2019 (COVID-19) affects respiratory, gastrointestinal, cardiovascular and other systems disease. Studies describing liver involvement and liver function test (LFT) abnormalities are sparse from our population. This study was undertaken to estimate the LFT abnormalities in patients with COVID-19 in a tertiary care set up in India. Methods: In this retrospective study conducted at a tertiary care centre in Mumbai, India, all consecutive patients with proven COVID-19 by reverse transcriptase-PCR from March 23 to October 31, 2020 were enrolled. Of the 3280 case records profiled, 1474 cases were included in the study. Clinical characteristics, biochemical parameters and outcomes were recorded. Results: Overall 681 (46%) patient had deranged LFTs. Hepatocellular type of injury was most common (93%). Patients with deranged LFTs had more probability of developing severe disease (P<0.001) and mortality (P<0.001). Advanced age (P<0.001), male gender (P<0.001), diabetes mellitus (P<0.001), lower oxygen saturation levels at admission (P<0.001), higher neutrophil-lymphocyte ratio (P<0.001), history of diabetes mellitus and cirrhosiss were associated with deranged LFTs. Acute liver injury was seen in 65 (4.3%) cases on admission and 57 (3.5%) cases during hospital stay. On multivariate analysis for predicting mortality, age >60 yr serum creatinine >2 mg%, PaO2/FiO2 ratio ≤200 and raised AST >50 IU/l (OR: 2.34, CI: 1.59-3.48, P<0.001) were found to be significant. Interpretation & conclusions: In COVID-19, LFT abnormalities were common, and derangement increased as severity progressed. The presence of deranged LFT worsens the clinical outcome and predicts in-hospital mortality.

Inhibitory effect of phytochemicals towards SARS-CoV-2 papain like protease (PLpro) proteolytic and deubiquitinase activity.

Recent studies have shown that RNA-dependent RNA polymerase (RdRp), 3-chymotrypsin-like protease (3CLpro), and papain-like protease (PLpro) are necessary for SARS-CoV-2 replication. Among these three enzymes, PLpro exhibits both proteolytic and deubiquitinase (DUB) activity and is responsible for disrupting the host's innate immune response against SARS-CoV-2. Because of this unique property of PLpro, we investigated the inhibitory effects of phytochemicals on the SARS-CoV-2 PLpro enzyme. Our data indicates that the phytochemicals such as catechin, epigallocatechin gallate (EGCG), mangiferin, myricetin, rutin, and theaflavin exhibited inhibitory activity with IC50 values of 14.2, 128.4, 95.3, 12.1, and 43.4, and 7.3 µM, respectively, towards PLpro proteolytic activity. However, the IC50 values of quercetin, oleuropein, and γ-mangostin are ambiguous. We observed that EGCG, mangiferin, myricetin, oleuropein, rutin, and theaflavin have also inhibited the DUB activity with IC50 values of 44.7, 104.3, 29.2, 131.5, 61.7, and 13.2 µM, respectively. Mechanistically, the ligand-protein interaction structural modeling suggests that mangiferin, EGCG, theaflavin, and oleuropein shows that these four ligands interact with Glu167, and Tyr268, however mangiferin and oleuropein showed very weak interaction with Glu167 as compared to EGCG, and theaflavin which reflects their low IC50 values for DUB activity. Our data indicate that the phytochemicals mentioned above inhibit the proteolytic and DUB activity of SARS-CoV-2 PLpro, thus preventing viral replication and promoting host innate immune response. However, the therapeutic potential of these phytochemicals needs to be validated by pre-clinical and clinical studies.

Neurobiology of traumatic brain injury.

Traumatic brain injury (TBI) involves structural damage to the brain regions causing death or disability in patients with lifelong sufferings. Accidental injuries to the brain, besides structural damage, if any, cause activation of various deleterious pathways leading to subsequent neuronal death and permanent dysfunction. However, immediate medical management/treatments could reduce the chances of disability and suffering to the patients. The objective of the current review is to review triggered molecular pathways following TBI and discuss possible targets that could restore brain functions. Understanding the pathologic process is always useful to device novel treatment strategies and may rescue the patient with TBI from death or associated co-morbidities. The current review significantly contributes to improve our understanding about the molecular pathways and neuronal death following TBI and helps us to provide possible targets that could be useful in the management/treatment of TBI.

Primary pancreatic tuberculosis with a duodenal fistula in an immunocompetent young man.

Tuberculosis (TB) is a common disease in developing countries that can virtually affect any organ in the body. The abdomen is one of the most common sites for extra-pulmonary tuberculosis. Primary Pancreatic tuberculosis (PPTB) is rare and can be clinically elusive. It is commonly encountered in immunodeficient individuals in regions endemic for TB. However, it is extremely rare in immunocompetent individuals with very few case reports in the literature. We describe a case of PPTB in an immunocompetent young man complicated with duodenal fistula. There was complete resolution of symptoms and the fistulous tract with a significant reduction of the size of the lesion on imaging after 6 months of anti-tubercular therapy (ATT).

Complete hemogram: simple and cost-effective in staging and predicting outcome in acute pancreatitis.

BACKGROUND: An important goal in management of acute pancreatitis (AP) is early prediction and recognition of disease severity. Various predictive scoring systems are in clinical use with their own limitations and there is always a quest for simple, practical, quantifiable, dynamic and readily available markers for predicting disease severity and outcome. Complete hemogram is routinely ordered in all patients with AP. In recent years red cell distribution width (RDW), neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR) and platelet lymphocyte ratio (PLR) have been found to be independent predictors of prognosis in various benign and malignant conditions. This prospective study evaluated complete hemogram based markers in AP. MATERIAL AND METHODS: Complete hemogram analysis was done and NLR, LMR, PLR values were calculated. Development of organ failure, the need for intensive care unit (ICU) admission and interventions, development of complications (local/systemic) and 100-day mortality were assessed. RESULTS: In this study 160 subjects of AP were included. Complete hemogram analysis was performed within 24 h after admission. C­reactive protein, RDW, NLR, PLR and bedside index of severity in acute pancreatitis (BISAP) values were higher in severe AP than moderate AP group than mild AP group, while LMR values were decreased in the corresponding severe, moderate and mild AP groups (p < 0.001). The NLR performed best for prediction of ICU admission, organ failure, interventions and mortality with area under receiver operating curve (AUROC) were 0.943, 0.940, 0.902 and 0.910, respectively. CONCLUSION: Hemogram based markers are simple, objective, dynamic and readily available. They can be considered in addition to conventional multifactorial scoring systems for prediction of outcome and prognosis of AP.

CEA, CA 15-3, and miRNA expression as potential biomarkers in canine mammary tumors.

The most often detected tumor in intact bitches is mammary tumors and represents a significant clinical problem throughout the world. Mammary neoplasms in canine have heterogeneous morphology, so the choice of the most appropriate biomarker is the biggest challenge in CMT detection. We performed a retrospective analysis and evaluated the canine cancer antigens and miRNA expression profiles as potential biomarkers. Sixty dogs based on histological examination divided into three groups, viz., dogs with a benign mammary tumor, malignant mammary tumor, and control/healthy. The CA 15-3 was found more sensitive than CEA but detection of both will increase sensitivity. miR-21 expression differed significantly in all three groups. miR-29b expression differed significantly between the control and benign group and control and malignant group. The miR-21 overexpression and miR-29b downregulation with CMT are associated with clinical stage and can be used as non-invasive diagnostic and prognostic biomarkers. Hence, evaluation of CA 15-3 along with CEA would be a non-invasive technique for detecting canine mammary tumors. Evaluation of deregulated circulating miR-21 could be a valuable prognostic marker for early detection of mammary tumors in canines while miR-29b can add sensitivity in the detection of the canine mammary tumors if evaluated with miR-21.

ß-lactam antibiotics to tame down molecular pathways of Alzheimer's disease.

Alzheimer's disease is a multifactorial disorder characterized by extracellular accumulation of amyloid-ß (Aß) and intracellular accumulations of neurofibrillary tangles. Numerous drug targets have been explored for therapeutic efficacy but failed to deliver successful treatments clinically. However, over the years our understanding of the disease pathophysiology increased significantly. Many of the novel targets which can cure or modify disease pathology are being explored preclinically as well as clinically. On contrarily, the drug discovery and development process is lengthy and the cost involved makes it difficult for faster translation of therapeutic outcomes. Therefore, repurposing existing drugs for a new therapeutic indication is considered a better approach and helps in the fast translation of therapeutic information. The existing drugs have well-proven records on their safety, pharmacokinetics, etc. In recent years, beta (ß)-lactam antibiotics have been repurposed for the management of neurodegenerative pathologies. Here in the current review, we have explored ß-lactam antibiotics, their target sites, molecular mechanisms, and their therapeutic potential in Alzheimer's disease.

Management of chyle leak in right side neck dissection: a rare case and review of literature (a case report).

Chyle leak is a well-recognized iatrogenic thoracic duct injury but a rare and serious complication of head and neck surgery affecting 1-2.5% of head and neck surgery dissections. It is potentially a life-threatening condition and management may be problematic and prolonged. Here we presented a rare case report of right sided chyle leak with its surgical management and review of literature. A 56-year-old patient with a complain of non-healing ulcer in the right buccal vestibule in the last 1-2 months reported to the outpatient department (OPD). After complete preoperative profile and counseling patient's consent was taken and wide local excision of lesion was done with bite composite resection with right hemimandibulectomy and maxillary alveolectomy till pterygoid plates, with right side selective neck dissection, level I-III followed by reconstruction with right side pectoralis major myofascial flap. Then the patient was on 5 days octreotide therapy. Regular post-operative follow-up was taken and no leak was noted further. In case of a chyle leak early diagnosis and aggressive treatment is essential to avoid local and systemic complications that prolong hospitalization.

The War against Tuberculosis: A Review of Natural Compounds and Their Derivatives.

Tuberculosis (TB), caused by the bacterial organism Mycobacterium tuberculosis, pose a major threat to public health, especially in middle and low-income countries. Worldwide in 2018, approximately 10 million new cases of TB were reported to the World Health Organization (WHO). There are a limited number of medications available to treat TB; additionally, multi-drug resistant TB and extensively-drug resistant TB strains are becoming more prevalent. As a result of various factors, such as increased costs of developing new medications and adverse side effects from current medications, researchers continue to evaluate natural compounds for additional treatment options. These substances have the potential to target bacterial cell structures and may contribute to successful treatment. For example, a study reported that green and black tea, which contains epigallocatechin gallate (a phenolic antioxidant), may decrease the risk of contracting TB in experimental subjects; cumin (a seed from the parsley plant) has been demonstrated to improve the bioavailability of rifampicin, an important anti-TB medication, and propolis (a natural substance produced by honeybees) has been shown to improve the binding affinity of anti-TB medications to bacterial cell structures. In this article, we review the opportunistic pathogen M. tuberculosis, various potential therapeutic targets, available therapies, and natural compounds that may have anti-TB properties. In conclusion, different natural compounds alone as well as in combination with already approved medication regimens should continue to be investigated as treatment options for TB.

Correction to: Embelin Attenuates Intracerebroventricular Streptozotocin-Induced Behavioral, Biochemical, and Neurochemical Abnormalities in Rats.

The original version of this article unfortunately missed to include the other affiliation of the first author Rimpi Arora as listed below.

Immunotherapies and Combination Strategies for Immuno-Oncology.

The advent of novel immunotherapies in the treatment of cancers has dramatically changed the landscape of the oncology field. Recent developments in checkpoint inhibition therapies, tumor-infiltrating lymphocyte therapies, chimeric antigen receptor T cell therapies, and cancer vaccines have shown immense promise for significant advancements in cancer treatments. Immunotherapies act on distinct steps of immune response to augment the body's natural ability to recognize, target, and destroy cancerous cells. Combination treatments with immunotherapies and other modalities intend to activate immune response, decrease immunosuppression, and target signaling and resistance pathways to offer a more durable, long-lasting treatment compared to traditional therapies and immunotherapies as monotherapies for cancers. This review aims to briefly describe the rationale, mechanisms of action, and clinical efficacy of common immunotherapies and highlight promising combination strategies currently approved or under clinical development. Additionally, we will discuss the benefits and limitations of these immunotherapy approaches as monotherapies as well as in combination with other treatments.