LSG vs OAGB: 7-Year Follow-up Data of a Randomised Control Trial and Comparative Outcome Based on BAROS Score.

BACKGROUND: This study aims to evaluate and compare long-term results of laparoscopic sleeve gastrectomy (LSG) and one anastomosis gastric bypass (OAGB) based on bariatric analysis reporting and outcome system (BAROS) score. MATERIALS AND METHODS: Patients operated for morbid obesity between 2013 and 2015 were randomised to LSG and OAGB groups. Based on inclusion and exclusion criteria, 201 patients (100 LSG and 101 OAGB) were analysed for changes in total body weight (TBW), body mass index (BMI), percent excess weight loss (%EWL), percent total weight loss (%TWL), QoL (quality of life) scores, comorbidity resolution and outcome based on BAROS at 7 years. RESULTS: Sixty-six LSG and 64 OAGB patients were followed up at 7 years. Mean pre-operative TBW and BMI were 119 ± 28.2 and 44.87 ± 7.71 for LSG group and 113.25 ± 23.74 and 44.71 ± 8.75 for OAGB group respectively. At 7 years after surgery, there was significant drop in mean TBW and BMI in both groups. Mean %EWL for LSG and OAGB patients was 50.78 ± 28.48 and 59.99 ± 23.32 and mean %TWL for LSG and OAGB patients was 23.22 ± 12.66 and 27.71 ± 12.27 respectively. Mean QoL scores at 7 years were significantly higher than the pre-operative scores and most of the patients in both groups had remission or improvement in their comorbidities. 68.76% OAGB patients had very good or excellent outcome on BAROS score while only 36.37% LSG patients had similar outcome. CONCLUSIONS: LSG and OAGB are successful bariatric procedures over the long term. OAGB outperforms LSG and has significantly higher %EWL and %TWL over the long term.

Neglected and locked anterior shoulder dislocation: functional outcomes and complications after open reduction and preservation of humeral head.

Background: Neglected and locked anterior shoulder dislocation is a rare problem that presents several treatment challenges. Our study aimed to evaluate the functional outcomes and postoperative complications after open reduction and head preservation surgery in patients with neglected and locked anterior shoulder dislocation. Methods: Ten patients (age 51 ± 22 years) with a follow-up of 27 months ± 7 months (range 24-40 months) were included in the study. The anteriorly dislocated humeral heads were open and reduced after an average neglect of 10 ± 15 months. The neglected dislocation was classified into two types by the severity of the injury. (1) Type 1: There were no associated severe injuries, and the humeral head was reduced in the glenoid cavity without take-down of the subscapularis (type 1a) (n = 5) or via take-down of the upper half of the subscapularis (type 1b) (n = 2). (2) Type 2: There were associated factors such as a greater tuberosity fracture (n = 2) or a grade 3/4 fatty infiltrated supraspinatus and infraspinatus muscles (n = 1). Complete removal of the subscapularis was necessary to reduce the humeral head. Results: The pain scores improved from a baseline value of 8 ± 1 to a final value of 1 ± 1 (P < .001), the absolute Constant score improved from a baseline value of 13 ± 8 to a final value of 69 ± 21 (P < .001), elevation range of motion (ROM) improved from a baseline value of 44° ± 43° to a final value of 123° ± 30° (P < .001), external rotation ROM improved from 0° ± 13° to 49° ± 12° (P < .001), and internal rotation ROM improved from sacroiliac joint ± 2 vertebra level to thoracic T11 ± 3 vertebrae level (P < .0001). The final shoulder subjective value was 77 ± 20 and was excellent in 3 patients, good in 5 patients, fair in 1, and poor in 1 patient. Major complications were observed in 30% (n = 3) of patients: persistent humeral head anterior subluxation in 20% (n = 2) of patients and superior migration of the humeral head in 10% (n = 1) of patients. Conclusion: Open reduction and head preservation in patients with neglected anterior dislocation led to good functional outcomes in 70% (as per Constant score) to 80% (as per shoulder subjective value) of the patients. However, we observed major complications such as persistent anterior subluxation (n = 2) and superior head migration (n = 1), leading to suboptimal functional outcomes in cases with associated factors such as a greater tuberosity fracture or severe fatty infiltrated cuff muscles.

Potential role of microRNAs in personalized medicine against hepatitis: a futuristic approach.

MicroRNAs (miRNAs) have been the subject of extensive research for many years, primarily in the context of diseases such as cancer. However, our appreciation of their significance in viral infections, particularly in hepatitis, has increased due to the discovery of their association with both the host and the virus. Hepatitis is a major global health concern and can be caused by various viruses, including hepatitis A to E. This review highlights the key factors associated with miRNAs and their involvement in infections with various viruses that cause hepatitis. The review not only emphasizes the expression profiles of miRNAs in hepatitis but also puts a spotlight on their potential for diagnostics and therapeutic interventions. Ongoing extensive studies are propelling the therapeutic application of miRNAs, addressing both current limitations and potential strategies for the future of miRNAs in personalized medicine. Here, we discuss the potential of miRNAs to influence future medical research and an attempt to provide a thorough understanding of their diverse roles in hepatitis and beyond.

Oral haemangiomas- Series of two case reports and review of management.

Haemangiomas are one of the most common of all human birth defects and are based on vascular tissues. These lesions are mainly identified into two groups which are named as (a) capillary and (b) cavernous haemangioma. Capillary haemangioma consists of small capillary vessels which show lobules formation. Cavernous haemangioma consists of large dilated vessels and they can reach to large sizes. Many treatment modalities are evaluated in which some modalities are successful and some are quite disappointing. Surgical excision, irradiation, CO2 freezing, sclerosing agents, cauterization, steroid therapy and watchful waiting are among the treatment methods evaluated. The treatment plan established for Haemangiomas must consider aspects such as size, location, lesion hemodynamics, patient's age and viability of the technique to be used. In the present series of two case reports, the management of haemangioma was done using two different modalities depending on their presentation so that major complications can be avoided and more attention should be paid to more conservative treatment modalities.

Tailored one anastomosis gastric bypass - Subgroup analysis of a randomised control trial based on bilio-pancreatic limb length with long-term results of 101 patients.

Background: : Ideal bilio-pancreatic limb (BPL) length is a highly debatable issue in one anastomosis gastric bypass (OAGB). Whether to use a tailored BPL or a fixed-length BPL needs to be answered. Materials and Methods: : One-hundred and one patients who have undergone tailored OAGB based on basal metabolic index (BMI) and type 2 diabetes mellitus (T2DM) were analysed. Sixty-three patients had BPL of 150 cm and 38 patients had BPL of 180 cm. Mean pre-operative BMI of BPL 150 and 180 cm groups were 39.73 and 51.92 kg/m2, respectively. Results: There was a significant drop in mean total body weight, BMI and excess body weight of both the groups at 1 year which persisted for 5 years post-operatively. The mean BMI of BPL 150 and BPL 180 cm group at 5 years was 29.17 and 32.88 kg/m2, respectively. Although mean percentage excess weight loss (%EWL) and percentage of excess BMI loss in the two groups was similar, the mean percentage total weight loss (%TWL) was significantly higher for the BPL 180 cm group. There was no difference between the two groups in the number of patients who had >50% EWL and >20% TWL. At 5 years of follow-up, the mean serum iron level was significantly low in BPL 180 cm group. There was a significant drop in mean haemoglobin A1c values postoperatively, with no difference between the two groups. Conclusions: Tailored BPL of 150 and 180 cm do not show any difference in the number of patients achieving >50% EWL or >20% TWL and so increasing limb length may not increase the number of good responders for weight loss. Although the resolution of T2DM and improvement of QoL score do not change significantly with increase in BPL length, mean serum iron levels may be lower with longer BPL.

Integrative Multiomics and Regulatory Network Analyses Uncovers the Role of OAS3, TRAFD1, miR-222-3p, and miR-125b-5p in Hepatitis E Virus Infection.

The hepatitis E virus (HEV) is a long-ignored virus that has spread globally with time. It ranked 6th among the top risk-ranking viruses with high zoonotic spillover potential; thus, considering its viral threats is a pressing priority. The molecular pathophysiology of HEV infection or the underlying cause is limited. Therefore, we incorporated an unbiased, systematic methodology to get insights into the biological heterogeneity associated with the HEV. Our study fetched 93 and 2016 differentially expressed genes (DEGs) from chronic HEV (CHEV) infection in kidney-transplant patients, followed by hub module selection from a weighted gene co-expression network (WGCN). Most of the hub genes identified in this study were associated with interferon (IFN) signaling pathways. Amongst the genes induced by IFNs, the 2'-5'-oligoadenylate synthase 3 (OAS3) protein was upregulated. Protein-protein interaction (PPI) modular, functional enrichment, and feed-forward loop (FFL) analyses led to the identification of two key miRNAs, i.e., miR-222-3p and miR-125b-5p, which showed a strong association with the OAS3 gene and TRAF-type zinc finger domain containing 1 (TRAFD1) transcription factor (TF) based on essential centrality measures. Further experimental studies are required to substantiate the significance of these FFL-associated genes and miRNAs with their respective functions in CHEV. To our knowledge, it is the first time that miR-222-3p has been described as a reference miRNA for use in CHEV sample analyses. In conclusion, our study has enlightened a few budding targets of HEV, which might help us understand the cellular and molecular pathways dysregulated in HEV through various factors. Thus, providing a novel insight into its pathophysiology and progression dynamics.

LSG vs MGB-OAGB: 5-Year Follow-up Data and Comparative Outcome of the Two Procedures over Long Term-Results of a Randomised Control Trial.

BACKGROUND: Bariatric surgery is a durable and effective way for the management of obesity and resolution of related comorbidities. The aim of this study is to evaluate the outcome of laparoscopic sleeve gastrectomy (LSG) and one-anastomosis gastric bypass (OAGB) over long term in a South Asian population. MATERIALS AND METHODS: This is a prospective randomised trial comparing the outcome of 100 and 101 LSG and OAGB patients respectively after 5-year follow-up. This study is in continuity with previous published papers with 1- and 3-year follow-up. 71 LSG and 73 OAGB patients followed at 5 years. The results of these patients were analysed and compared in terms of %EWL, comorbidity resolution and quality of life (QoL) at 5 years. Bariatric analysis reporting and outcome system (BAROS) was used to assess the outcome of patients. RESULTS: At 5-year follow-up, both LSG and OAGB patients performed well and patients had significant improvement in BMI (kg/m2). The mean preoperative BMI of LSG and OAGB patients was 44.89 ± 7.94 and 45.32 ± 8.24, and their mean BMI at 5 years was 33.41 ± 6.02, 30.80 ± 3.40 respectively. At 5 years, %EWL was 55.95 ± 27.01 and 65.28 ± 13.98 for LSG and OAGB patients respectively. The QoL score of LSG and OAGB patients was 1.86 ± 0.56 and 2.35 ± 0.41 while comorbidity score was 1.84 ± 0.68 and 2.24 ± 0.62 respectively at 5 years. CONCLUSIONS: Both LSG and OAGB are effective bariatric procedures over long term with respect to weight loss, comorbidity resolution and improvement in QoL. OAGB is significantly better than LSG in all the three parameters at 5 years.

MGB-OAGB: Effect of Biliopancreatic Limb Length on Nutritional Deficiency, Weight Loss, and Comorbidity Resolution.

INTRODUCTION: Mini gastric bypass-one anastomosis gastric bypass (MGB-OAGB) has been approved as a mainstream metabolic/bariatric procedure by IFSO. Still there are lots of concerns regarding nutritional deficiency after MGB-OAGB. The purpose of this retrospective analysis is to evaluate the effect of biliopancreatic limb (BPL) length on weight loss, comorbidity resolution, and nutritional deficiencies in patients 1 year after MGB-OAGB and to find suitable BPL length. MATERIAL AND METHODS: One hundred and one patients who underwent MGB-OAGB were divided into three groups of 150 cm, 180 cm, and 250 cm depending on the length of BPL bypassed. The nutritional parameters (vitamin D3, vitamin B12, serum iron, serum ferritin, total protein, serum albumin, serum globulin), anthropometric measurements (weight, BMI), and comorbidity resolution (T2DM, hypertension) were compared between the three groups at 1-year follow-up. RESULTS: There was statistically significant difference in number of patients having deficiencies in all the nutritional parameters except globulin between 150 cm and 250 cm groups (P < 0.05). While on comparing 180- and 250-cm group, a statistically significant difference was present in vitamin D3, vitamin B12, and total protein (P < 0.05) only. The difference was statistically insignificant between the three groups on T2DM, hypertension resolution, and %EWL but TWL between 150 cm vs 180 cm and 150 cm vs 250 cm showed significant difference. CONCLUSION: A 150-cm BPL length is adequate with very minimal nutritional complications and good results. A 180-cm BPL can be used in super obese while a 250-cm BPL should be used with utmost care as it results in significant nutritional deficiencies.

Metabolic Enhancer Piracetam Attenuates the Translocation of Mitochondrion-Specific Proteins of Caspase-Independent Pathway, Poly [ADP-Ribose] Polymerase 1 Up-regulation and Oxidative DNA Fragmentation.

Piracetam, a nootropic drug, has been clinically used for decades; however, its mechanism of action still remains enigmatic. The present study was undertaken to evaluate the role of mitochondrion-specific factors of caspase-independent pathway like apoptotic-inducing factor (AIF) and endonuclease-G (endo-G) in piracetam-induced neuroprotection. N2A cells treated with lipopolysaccharide (LPS) exhibited significant cytotoxicity, impaired mitochondrial activity, and reactive oxygen species generation which was significantly attenuated with piracetam co-treatment. Cells co-treated with LPS and piracetam exhibited significant uptake of piracetam in comparison to only piracetam-treated cells as estimated by liquid chromatography-mass spectrometry (LC-MSMS). LPS treatment caused significant translocation of AIF and endonuclease-G in neuronal N2A cells which were significantly attenuated with piracetam co-treatment. Significant over-expression of proinflammatory cytokines was also observed after treatment of LPS to cells which was inhibited with piracetam co-treatment demonstrating its anti-inflammatory property. LPS-treated cells exhibited significant oxidative DNA fragmentation and poly [ADP-ribose] polymerase-1 (PARP-1) up-regulation in nucleus, both of which were attenuated with piracetam treatment. Antioxidant melatonin but not z-VAD offered the inhibited LPS-induced DNA fragmentation indicating the involvement of oxidative DNA fragmentation. Further, we did not observe the altered caspase-3 level after LPS treatment initially while at a later time point, significantly augmented level of caspase-3 was observed which was not inhibited with piracetam treatment. In total, our findings indicate the interference of piracetam in mitochondrion-mediated caspase-independent pathway, as well as its anti-inflammatory and antioxidative properties. Graphical Abstract Graphical abstract indicating the novel interference of metabolic enhancer piracetam (P) in neuronal death mechanisms.

Minocycline diminishes the rotenone induced neurotoxicity and glial activation via suppression of apoptosis, nitrite levels and oxidative stress.

The study was conducted to evaluate the effect of minocycline against pesticide rotenone induced adverse effects in different rat brain regions. Assessment of oxidative stress, nitrite levels, degenerating neurons and level of cleaved caspase-3 was done in frontal cortex, mid brain, hippocampus and striatum regions of rat brain. In addition the expression profile of neuronal (MAP2), astrocytes (GFAP) and microglia (cd11b) markers was done after treatments. Rotenone induced DNA fragmentation was also assessed in all studied rat brain regions by utilizing comet assay. Rotenone administration caused significantly decreased level of glutathione along with increased level of nitrite and lipid peroxidation. Significant oxidative and nitrosative stress was also observed after rotenone administration which was considerably inhibited in minocycline treated rats in time dependent manner. Fluorojade staining and levels of cleaved caspase 3 showed the degeneration of neurons and apoptosis respectively in studied rat brain regions which were further inhibited with minocycline treatment. Rotenone administration caused significantly increased reactivity of astrocytes, microglia and altered neuronal morphology in rat brain regions which was also partially restored with minocycline treatment. In conclusion, present study showed that minocycline treatment attenuated the rotenone induced oxidative stress, nitrite level, degeneration of neurons, augmented glial reactivity and apoptosis.

Effectiveness of Phytoactive Molecules on Transcriptional Expression, Biofilm Matrix, and Cell Wall Components of Candida glabrata and Its Clinical Isolates.

Toxicity challenges by antifungal arsenals and emergence of multidrug resistance scenario has posed a serious threat to global community. To cope up with this alarming situation, phytoactive molecules are richest, safest, and most effective source of broad spectrum antimicrobial compounds. In the present investigation, six phytoactive molecules [cinnamaldehyde (CIN), epigallocatechin, vanillin, eugenol (EUG), furanone, and epigallocatechin gallate] were studied against Candida glabrata and its clinical isolates. Among these, CIN and EUG which are active components of cinnamon and clove essential oils, respectively, exhibited maximum inhibition against planktonic growth of C. glabrata at a concentration of 64 and 128 µg mL-1, respectively. These two molecules effectively inhibited and eradicated approximately 80% biofilm of C. glabrata and its clinical isolates from biomaterials. CIN and EUG increased reactive oxygen species generation, cell lysis, and ergosterol content in plasma membrane and reduced virulence attributes (phospholipase and proteinase) as well as catalase activity of C. glabrata cells. Reduction of mitochondrial membrane potential with increased release of cytochrome c from mitochondria to cytosol indicated initiation of early apoptosis in CIN- and EUG-treated C. glabrata cells. Transcriptional analysis showed that multidrug transporter (CDR1) and ergosterol biosynthesis genes were downregulated in the presence of CIN, while getting upregulated in EUG-treated cells. Interestingly, genes such as 1,3-ß-glucan synthase (FKS1), GPI-anchored protein (KRE1), and sterol importer (AUS1) were downregulated upon treatment of CIN/EUG. These results provided molecular-level insights about the antifungal mechanism of CIN and EUG against C. glabrata including its resistant clinical isolate. The current data established that CIN and EUG can be potentially formulated in new antifungal strategies.

Involvement of glucose related energy crisis and endoplasmic reticulum stress: Insinuation of streptozotocin induced Alzheimer's like pathology.

The present study was conducted to correlate the cellular and molecular alterations in Alzheimer's pathology employing streptozotocin (STZ) induced experimental rat model. The STZ was administered in rat brain bilaterally by intracerebroventricular route using stereotaxic surgery followed by donepezil dosing. The Alzheimer's related pathological marker like acetylcholinesterase (AChE) activity, tau phosphorylation and amyloid aggregation were observed after STZ administration. STZ treatment showed decreased glucose and glucose transporters (GLUT) level along with augmented level of calcium in both cortical and hippocampal regions of rat brain. Increased calcium level may correlate with endoplasmic reticulum (ER) stress and significantly increased expression of ER stress markers like GRP78, GADD and caspase-12 were observed in STZ treated rat brain. Cellular communication was also affected by STZ administration as observed by increased expression connexin 43. With this view the activation of astrocytes and microglia was also assessed and observed by augmented GFAP and cd11b expression which were partially inhibited with donepezil treatment. The significantly increased level of degenerating neurons, caspase-3 and DNA fragmentation was also observed in rat brain regions which were not inhibited with donepezil treatment and validating the clinical observations. In conclusion, study indicated the STZ induced occurrence of Alzheimer's pathology. Further, STZ administration also caused depleted glucose level, inhibited mitochondrial activity, augmented calcium levels, ER stress, altered cellular communication and neuronal death which were partially attenuated with donepezil treatment.

Endoplasmic Reticulum Stress Instigates the Rotenone Induced Oxidative Apoptotic Neuronal Death: a Study in Rat Brain.

The present study was conducted to evaluate the involvement of endoplasmic reticulum stress in rotenone-induced oxidative neuronal death in rat brain. Rotenone (6 µg/3 µl) was administered intranigrally, unilaterally (right side) in SD rat brain. Neuronal morphology, expression level of tyrosine hydroxylase (TH) and endoplasmic reticulum (ER) stress markers like glucose-regulated protein 78 (GRP78), growth arrest and DNA damage-inducible gene 153 (GADD153), eukaryotic translation initiation factor 2α (p-eIF2α/eIF2α) and cleaved caspase-12 were estimated in the rat brain. Levels of reactive oxygen species (ROS), reduced glutathione (GSH) and enzymatic activities of glutathione peroxidase (GPx) and glutathione reductase (GRd) were estimated to assess the rotenone induced oxidative stress. Apoptotic death of neurons was assessed by estimating the mRNA level of caspase-3. Rotenone administration caused altered neuronal morphology, decreased expression of TH, augmented ROS level, decreased level of GSH and decreased activities of GPx and GRd enzymes which were significantly attenuated with the pretreatment of ER stress inhibitor, salubrinal (1 mg/kg, intraperitoneal). Significantly increased levels of GRP78, GADD, dephosphorylated eIF2α and cleaved caspase-12 was also observed after rotenone administration, which was inhibited with the pretreatment of salubrinal. Rotenone-induced increased mRNA level of caspase-3 was also attenuated by pretreatment of salubrinal. Findings suggested that salubrinal treatment significantly inhibited the rotenone-induced neurotoxicity implicating that ER stress initiates the rotenone-induced oxidative stress and neuronal death.

Endoplasmic Reticulum Stress Plays a Key Role in Rotenone-Induced Apoptotic Death of Neurons.

Rotenone, a pesticide, causes neurotoxicity via the mitochondrial complex-I inhibition. The present study was conducted to evaluate the role of endoplasmic reticulum (ER) stress in rotenone-induced neuronal death. Cell viability, cytotoxicity, reactive oxygen species (ROS) generation, nitrite level, mitochondrial membrane potential (MMP), and DNA damage were assessed in rotenone-treated neuro-2A cells. Protein levels of ER stress markers glucose regulated protein 78 (GRP78), growth arrest- and DNA damage-inducible gene 153 (GADD153), and phosphorylation of eukaryotic translation initiation factor 2 subunit α (eIF2-α) were estimated to assess the ER stress. To confirm the apoptotic death of neurons, mRNA levels of caspase-9, caspase-12 and caspase-3 were estimated. Further, to confirm the involvement of ER stress, neuro-2A cells were pretreated with ER stress inhibitor salubrinal. Co-treatment of antioxidant melatonin was also given to assess the role of oxidative stress in rotenone-induced apoptosis. Rotenone (0.1, 0.5, and 1 µM) treatment to neurons caused significantly decreased cell viability, increased cytotoxicity, increased ROS generation, increased expression of GRP78 and GADD, DNA damage and activation of caspase-12 and caspase-3 which were significantly attenuated by pretreatment of salubrinal (25 µM). Rotenone-induced dephosphorylation of eIF2α was also inhibited with salubrinal treatment. However, pretreatment of salubrinal did not affect the rotenone-induced increased nitrite levels, decreased MMP and caspase-9 activation. Co-treatment of antioxidant melatonin (1 mM) did not offer attenuation against rotenone-induced increased expression of caspase-9, caspase-12 and caspase-3. In conclusion, results indicated that ER stress plays a key role in rotenone-induced neuronal death, rather than oxidative stress. Graphical Abstract Pictorial presentation showed the involvement of endoplasmic reticulum (ER) stress, increased reactive oxygen species (ROS), nitrite level, decreased mitochondrial membrane potential (MMP), caspase activation and DNA damage in neuronal cells after rotenone treatment. ER stress inhibitor-salubrinal showed significant attenuation against most of the rotenone-induced adverse effects reflecting its key involvement in rotenone-induced neuronal death.

Astrocyte activation and neurotoxicity: A study in different rat brain regions and in rat C6 astroglial cells.

The present study was conducted to investigate the effect of rotenone on astrocytes activation, their viability and its effect on neuronal death in different brain regions. Rotenone was injected in rat brain by intracerebroventricularly (bilateral) route at dose of 6 µg and 12 µg. In vitro C6 cells were treated with rotenone at concentration of 0.1, 0.25, 0.5, 1 and 2 µM. Rotenone administration to rat brain caused significant astrocytes activation in frontal cortex, cerebellum, cerebellar nucleus, substantia nigra, hypothalamus and hippocampus regions of the rat brain. Rotenone administration also led to significant degeneration of cells in all the studied regions along with altered nuclear morphology assessed by hematoxylin-eosin and cresyl violet staining. Histological staining showed the significantly decreased number of cells in all the studied regions except cerebellar nucleus in dose and time dependant manner. Rotenone administration in the rat brain also caused significant decrease in glutathione levels and augmented nitrite levels. In vitro treatment of rotenone to astrocytic C6 cells caused significantly increased expression of glial fibrillar acidic protein (GFAP) and decreased viability in dose and time dependent manner. Rotenone treatment to C6 cells exhibited significant generation of reactive oxygen species, augmented nitrite level, impaired mitochondrial activity, apoptotic chromatin condensation and DNA damage in comparison to control cells. Findings showed that oxidative stress play a considerable role in rotenone induced astrocyte death that was attenuated with co-treatment of antioxidant melatonin. In conclusion, results showed that rotenone caused significant astrocytes activation, altered nuclear morphology, biochemical alteration and apoptotic cell death in different rat brain regions. In vitro observations in C6 cells showed that rotenone treatment exhibited oxidative stress mediated apoptotic cell death, which was attenuated with co treatment of melatonin.

Pseudocarcinomatous Hyperplasia of the Fallopian Tubes which was Associated with Female Genital Tract Tuberculosis, Histologically Mimicking Tubal Adenocarcinoma: A Diagnostic Challenge.

The benign proliferative and reactive processes of the fallopian tubes which are a result of female genital tract tuberculosis can mimick malignant neoplasms, both clinically and pathologically. 'Pseudocarcinomatous hyperplasia' is a term which is applied to the florid form of epithelial hyperplasia with atypical features, that mimicks tubal adenocarcinoma. It may be encountered in the tuberculous and the non tuberculous forms of chronic salphingitis. We are reporting a case of a 30 years old female who presented to our institute with complaints of vaginal discharge and fever. She underwent panhysterectomy for uterine fibroids. Both her fallopian tubes revealed features of florid atypical epithelial hyperplasia, along with widespread caseating granulomatas. Ziehl Neelsen (ZN) staining of the lesion for acid fast bacilli (AFB) was positive. A diagnosis of pseudocarcinomatous hyperplasia of the fallopian tubes which was associated with female genital tract tuberculosis, which histologically mimicked tubal adenocarcinoma was made, which posed a diagnostic dilemma.

Rotenone-induced apoptosis and role of calcium: a study on Neuro-2a cells.

Rotenone causes cytotoxicity in astrocytic cell culture by glial activation, which is linked to free radical generation. The present study is an investigation to explore whether rotenone could also cause cellular toxicity in mouse neuroblastoma cells (Neuro-2a) under treatment similar to astroglial cells. The effect of rotenone (0.1, 1, and 10 µM) on mitochondrial dehydrogenase enzyme activity by MTT reduction assay, PI uptake, total reactive oxygen species (ROS)/superoxide levels, nitrite levels, extent of DNA damage (by comet assay), and nuclear morphological alteration by Hoechst staining was studied. Caspase-3 and Ca⁺²/calmodulin-dependent protein kinase II (CaMKIIα) gene expression was determined to evaluate the apoptotic cell death and calcium kinase, respectively. Calcium level was estimated fluorometrically using fura-2A stain. Rotenone decreased mitochondrial dehydrogenase enzyme activity and generated ROS, superoxide, and nitrite. Rotenone treatment impaired cell intactness and nuclear morphology as depicted by PI uptake and chromosomal condensation of Neuro-2a cells, respectively. In addition, rotenone resulted in increased intracellular Ca⁺² level, caspase-3, and CaMKIIα expression. Furthermore, co-exposure of melatonin (300 µM), an antioxidant to cell culture, significantly suppressed the rotenone-induced decreased mitochondrial dehydrogenase enzyme activity, elevated ROS and RNS. However, melatonin was found ineffective to counteract rotenone-induced increased PI uptake, altered morphological changes, DNA damage, elevated Ca⁺², and increased expression of caspase-3 and CaMKIIα. The study indicates that intracellular calcium rather than oxidative stress is a major factor for rotenone-induced apoptosis in neuronal cells.