Cardiac amyloidosis: A diagnostic challenge.

Cardiac amyloidosis is indeed a condition characterized by the deposition of amyloid proteins in the myocardium, leading to thickening and stiffening of the heart muscle. These abnormal protein deposits can interfere with the heart's normal functioning and may pose diagnostic challenges due to its varied clinical presentation and resemblance to other heart condition. Here, we present a case of 55-year-old female patient of uncontrolled hypertensions for 15 years. About 15 years ago, she presented with chest pain and was diagnosed with cardiomyopathy (CM) characterized by low left ventricle (LV) function of unknown cause. Despite being on antihypertensive treatment, the patient continued to experience chest heaviness with persistent elevate blood pressure. An echocardiogram revealed increased LV septal wall thickness, valvular thickening, and biatrial dilation. Subsequently, cardiac magnetic resonance imaging (CMR) was performed, which revealed left atrium enlargement and asymmetrical myocardial wall thickening, particularly at the septum. White blood axial image revealed thickened inter atrial septum, while late gadolinium enhancement (LGE) magnetic resonance (LGE MR) images showed patchy LGE at the base relative to the apex of the myocardium, highlighting the base-to-apex gradient, subendocardial pattern enhancement at apical lateral wall, and transmural pattern enhancement of the mid anteroseptal and inferoseptal wall. Additionally, a short axis time to invert T1 scout image of left ventricle displayed an abnormal nulling pattern initially in the myocardium, followed by the blood pool, and finally the spleen. These findings collectively led to the diagnosis of cardiac amyloidosis.

Upregulation of XRCC1 DNA Repair Gene, Interleukin-8, and Bcl-2 Antiapoptotic Gene Levels in Kurdish Patients with Gastric Adenocarcinoma.

Gastric cancer (GC) is one of the deadliest tumors due to its competence to invade and metastasize. The DNA repair gene (XRCC1), interleukin-8 (IL-8) gene, and B-cell lymphoma 2 (Bcl-2) gene play a crucial role in the development and progression of GC. This study aimed to evaluate the expression of these target genes in GC patients in the Kurdistan region of Iraq. Gastric cancer tissues were collected from 29 patients diagnosed with gastric adenocarcinoma that underwent gastric resection, and 21 tissue samples were obtained from healthy patients that underwent gastroscopy. The gastric tissues were collected in different hospitals in Erbil and Sulaymaniyah cities in the Kurdistan region of Iraq. Moreover, the data regarding Helicobacter pylori, age, gender, and stage of the disease were recorded and analyzed using GraphPad Prism. The gene expression levels of XRCC1, IL-8, and Bcl-2 from gastric tissue were studied by real-time quantitative polymerase chain reaction. The results showed that H. pylori infection was equally distributed among males and females in the tissues of gastric patients, while most of the H. pylori-negative patients were females. It is also found that gastric patients aged 30-60 years old are more commonly tested for the H. pylori test. Accordingly, in this study, patients diagnosed with gastric inflammation more often tested positive for H. pylori, while patients diagnosed with gastric cancer tested negative for this infection. Additionally, it was found that the target genes (XRCC1, IL-8, and Bcl-2) were significantly upregulated in GC patients, compared to the healthy group. Finally, the result revealed that XRCC1, IL-8, and Bcl-2 were upregulated in the Kurdish patients with GC, compared to the healthy control group. Targeting XRCC1, IL-8, and Bcl-2 genes can be an interesting field and promising strategy for cancer treatment.

Reprocessing and reuse of dialyzers: A technological solution for balancing cost and quality in lower and middle-income countries.

Hemodialysis is the commonest kidney replacement therapy (KRT) globally and rapidly growing in developing countries, while in developed countries it is reaching a plateau. The penetration of hemodialysis (HD) varies widely among countries and is largely influenced by socioeconomics, healthcare financing, particularly by government, local infrastructure, healthcare workforce, health system characteristics, and affordability of the population. Biomedical equipment, consumables, disposables, and labor are major cost drivers of KRT. Implementing strategies to balance cost and quality of care is an arduous task for health care planning, delivery, and patient care in low- and middle-income countries. In this context, the cost of dialyzers which form a significant component of the recurring cost of HD can be reduced by reuse after appropriate reprocessing. But this practice is largely abandoned in developed countries because of concerns of safety. However, the evidence against the reuse of modern dialyzers is not robust and certainly not based on well-designed randomized trials. The industrialization of dialysis delivery, the interests of equipment manufacturers and the nature of dialysis delivery have propelled single use of dialyzers. In this context, developing countries needing to expand HD services access at low cost are caught at crossroads. Process improvements are needed to standardize reprocessing that prioritizes safety while maintaining effectiveness. Recent advances in mobile and internet technologies could make this an achievable reality. We propose such an approach that would ensure treatment effectiveness, patient and healthcare provider safety, efficient resource utilization, and cost control.

Hepatic protein kinase Cbeta deficiency mitigates late-onset obesity.

Although aging is associated with progressive adiposity and a decline in liver function, the underlying molecular mechanisms and metabolic interplay are incompletely understood. Here, we demonstrate that aging induces hepatic protein kinase Cbeta (PKCß) expression, while hepatocyte PKCß deficiency (PKCßHep-/-) in mice significantly attenuates obesity in aged mice fed a high-fat diet. Compared with control PKCßfl/fl mice, PKCßHep-/- mice showed elevated energy expenditure with augmentation of oxygen consumption and carbon dioxide production which was dependent on ß3-adrenergic receptor signaling, thereby favoring negative energy balance. This effect was accompanied by induction of thermogenic genes in brown adipose tissue (BAT) and increased BAT respiratory capacity, as well as a shift to oxidative muscle fiber type with an improved mitochondrial function, thereby enhancing oxidative capacity of thermogenic tissues. Furthermore, in PKCßHep-/- mice, we determined that PKCß overexpression in the liver mitigated elevated expression of thermogenic genes in BAT. In conclusion, our study thus establishes hepatocyte PKCß induction as a critical component of pathophysiological energy metabolism by promoting progressive hepatic and extrahepatic metabolic derangements in energy homeostasis, contributing to late-onset obesity. These findings have potential implications for augmenting thermogenesis as a means of combating aging-induced obesity.

The Utility of Peptide Ligand-Functionalized Liposomes for Subcutaneous Drug Delivery for Arthritis Therapy.

Liposomes and other types of nanoparticles are increasingly being explored for drug delivery in a variety of diseases. There is an impetus in the field to exploit different types of ligands to functionalize nanoparticles to guide them to the diseased site. Most of this work has been conducted in the cancer field, with relatively much less information from autoimmune diseases, such as rheumatoid arthritis (RA). Furthermore, in RA, many drugs are self-administered by patients subcutaneously (SC). In this context, we have examined the attributes of liposomes functionalized with a novel joint-homing peptide (denoted ART-1) for arthritis therapy using the SC route. This peptide was previously identified following phage peptide library screening in the rat adjuvant arthritis (AA) model. Our results show a distinct effect of this peptide ligand on increasing the zeta potential of liposomes. Furthermore, liposomes injected SC into arthritic rats showed preferential homing to arthritic joints, following a migration profile in vivo similar to that of intravenously injected liposomes, except for a less steep decline after the peak. Finally, liposomal dexamethasone administered SC was more effective than the unpackaged (free) drug in suppressing arthritis progression in rats. We suggest that with suitable modifications, this SC liposomal treatment modality can be adapted for human RA therapy.

Hydatid Disease: A Radiological Pictorial Review of a Great Neoplasms Mimicker.

Hydatid cyst is a common name for the larval stage of a tapeworm species of Echinococcus granulosus, which is transmitted from animals to humans via the fecal-oral route. Hydatid cysts predominantly affect the liver (75%), followed by the lung (15%), and they can affect many organs in the human body. Medical imaging modalities are the keystone for the diagnosis of hydatid cysts with high sensitivity and specificity. Ultrasound imaging with high resolution is the first choice for diagnosis, differential diagnosis, staging, establishing a role in interventional management, and follow-up, and it can differentiate Type I hydatid cysts from simple liver cysts. Unenhanced computed tomography (CT) is indicated where or when an ultrasound is unsatisfactory, such as with chest or brain hydatid cysts, when detecting calcification, and in obese patients. Magnetic resonance imaging (MRI) is superior for demonstrating cyst wall defects, biliary communication, neural involvement, and differentiating hydatid cysts from simple cysts using diffusion-weighted imaging (DWI) sequences. According to the phase of growth, hydatid cysts occur in different sizes and shapes, which may mimic benign or malignant neoplasms and may create diagnostic challenges in some cases. Hydatid cysts can mimic simple cysts, choledochal cysts, Caroli's disease, or mesenchymal hamartomas of the liver. They can mimic lung cystic lesions, mycetoma, blood clots, Rasmussen aneurysms, and even lung carcinomas. Differential diagnosis can be difficult for arachnoid cysts, porencephalic cysts, pyogenic abscesses, and even cystic tumors of the brain, and can create diagnostic dilemmas in the musculoskeletal system.

Marginal Bone Loss Evaluation Postdental Implants Placed with Platelet-Rich Plasma: An Original Research.

Introduction: Various materials are used to improve the longevity of the dental implants. In our study, we assessed the marginal bone loss around dental implants after implantation with platelet-rich plasma. Materials and Methods: We conducted a prospective clinical study among 200 subjects who were grouped equally as those with and without the application of PRF in the implantation. The radiographic and clinical features for the marginal bone loss were assessed and compared keeping P < 0.05 as statistically significant. Results: We observed no significant variation between the groups for the mobility, bleeding on probing, plaque index, and marginal bone loss. Conclusion: We can conclude that the application of PRP concentrate did not significantly affect the marginal bone loss in the dental implantation.

Hydroxychloroquine plus personal protective equipment versus personal protective equipment alone for the prevention of laboratory-confirmed COVID-19 infections among healthcare workers: a multicentre, parallel-group randomised controlled trial from India.

OBJECTIVES: To determine whether hydroxychloroquine when used with personal protective equipment reduces the proportion of laboratory-confirmed COVID-19 among healthcare workers in comparison to the use of personal protective equipment alone. DESIGN: Multicentre, parallel-group, open-label randomised trial. Enrolment started on 29 June 2020 and stopped on 4 February 2021. Participants randomised in HydrOxychloroquine Prophylaxis Evaluation were followed for 6 months. SETTING: 9 hospitals across India. PARTICIPANTS: Healthcare workers in an environment with exposure to COVID-19 were randomised in a 1:1 ratio to hydroxychloroquine plus use of personal protective equipment or personal protective equipment alone. 886 participants were screened and 416 randomised (213 hydroxychloroquine arm and 203 personal protective equipment). INTERVENTION: Participants in intervention arm received 800 mg of hydroxychloroquine on day of randomisation and then 400 mg once a week for 12 weeks in addition to the use of personal protective equipment. In the control arm, participants continued to use personal protective equipment alone. MAIN OUTCOME: Proportion of laboratory-confirmed COVID-19 in the 6 months after randomisation. RESULTS: Participants were young (mean age 32.1 years, SD 9.1 years) with low-comorbid burden. 47.4% were female. In the 6 months after randomisation (primary analysis population=413), 11 participants assigned to the hydroxychloroquine group and 12 participants assigned to the standard practice group met the primary endpoint (5.2% vs 5.9%; OR 0.85, 95% CI 0.35 to 2.07, p=0.72). There was no heterogeneity of treatment effect in any prespecified subgroup. There were no significant differences in the secondary outcomes. The adverse event rates were 9.9% and 6.9% in the hydroxychloroquine and standard practice arms, respectively. There were no serious adverse events in either group. CONCLUSIONS AND RELEVANCE: Hydroxychloroquine along with personal protective equipment was not superior to personal protective equipment alone on the proportion of laboratory-confirmed COVID-19. Definitive conclusions are precluded as the trial stopped early for futility, and hence was underpowered. TRIAL REGISTRATION NUMBER: CTRI/2020/05/025067.

Risks of khat chewing on the cardiovascular, nervous, gastrointestinal, and genitourinary systems: A narrative review.

Khat is an evergreen plant and its fresh green leaves and buds are chewed for several hours a day for its psychostimulant response. This study aimed to review the effects of khat chewing on the body. PubMed was searched for literature on the different aspects of khat chewing to summarize its effects on different body systems. The major effects of khat chewing are those on the cardiovascular system including increased blood pressure, increased heart rate, and increased risk of myocardial infarction. It causes insomnia, stress, depression, hallucination, and increased risk of brain stroke. It causes dental caries, bad oral hygiene, periodontitis, increased oral mucosal ulcers, and increased gingival bleeding and recession. Khat chewing causes loss of appetite, gastritis, constipation, and hemorrhoids, and increased risk of hepatotoxicity and liver cirrhosis. Ultimately, it causes weak micturition, decreased sperm motility and count, and low birth-weight offspring in khat chewing mothers. The published articles about khat chewing in journals indexed in the PubMed was reviewed. Inclusion criteria involved each article available with English language and have a reported new effect of khat chewing.

The Diagnostic Deceiver: Radiological Pictorial Review of Tuberculosis.

Tuberculosis (TB) is a bacterial infection with Mycobacterium tuberculosis; it is a public health problem worldwide and one of the leading causes of mortality. Since December 2019, the COVID-19 pandemic has created unprecedented health challenges and disrupted the TB health services, especially in high-burden countries with ever-increasing prevalence. Extrapulmonary and even pulmonary TB are an important cause of nonspecific clinical and radiological manifestations and can masquerade as any benign or malignant medical case, thus causing disastrous conditions and diagnostic dilemmas. Clinical manifestations and routine laboratory tests have limitations in directing physicians to diagnose TB. Medical-imaging examinations play an essential role in detecting tissue abnormalities and early suspecting diagnosis of TB in different organs. Radiologists and physicians should be familiar with and aware of the radiological manifestations of TB to contribute to the early suspicion and diagnosis of TB. The purpose of this article is to illustrate the common radiologic patterns of pulmonary and extrapulmonary TB. This article will be beneficial for radiologists, medical students, chest physicians, and infectious-disease doctors who are interested in the diagnosis of TB.

The Anti-Inflammatory and Immunomodulatory Activities of Natural Products to Control Autoimmune Inflammation.

Inflammation is an integral part of autoimmune diseases, which are caused by dysregulation of the immune system. This dysregulation involves an imbalance between pro-inflammatory versus anti-inflammatory mediators. These mediators include various cytokines and chemokines; defined subsets of T helper/T regulatory cells, M1/M2 macrophages, activating/tolerogenic dendritic cells, and antibody-producing/regulatory B cells. Despite the availability of many anti-inflammatory/immunomodulatory drugs, the severe adverse reactions associated with their long-term use and often their high costs are impediments in effectively controlling the disease process. Accordingly, suitable alternatives are being sought for these conventional drugs. Natural products offer promising adjuncts/alternatives in this regard. The availability of specific compounds isolated from dietary/medicinal plant extracts have permitted rigorous studies on their disease-modulating activities and the mechanisms involved therein. Here, we describe the basic characteristics, mechanisms of action, and preventive/therapeutic applications of 5 well-characterized natural product compounds (Resveratrol, Curcumin, Boswellic acids, Epigallocatechin-3-gallate, and Triptolide). These compounds have been tested extensively in animal models of autoimmunity as well as in limited clinical trials in patients having the corresponding diseases. We have focused our description on predominantly T cell-mediated diseases, such as rheumatoid arthritis, multiple sclerosis, Type 1 diabetes, ulcerative colitis, and psoriasis.

Anti-IgE effect of small-molecule-compound arctigenin on food allergy in association with a distinct transcriptome profile.

BACKGROUND: Excessive production of IgE plays a major role in the pathology of food allergy. In an attempt to identify anti-IgE natural products, Arctium Lappa was one of the most effective herbs among approximately 300 screened medicinal herbs. However, little is known about its anti-IgE compounds. OBJECTIVE: To identify compounds from Arctium Lappa for targeted therapy on IgE production and explore their underlying mechanisms. METHODS: Liquid-liquid extraction and column chromatographic methods were used to purify the compounds. IgE inhibitory effects were determined on IgE-producing human myeloma U266 cells, peanut-allergic murine model and PBMCs from food-allergic patients. Genes involved in IgE inhibition in PBMCs were studied by RNA sequencing. RESULTS: The main compounds isolated were identified as arctiin and arctigenin. Both compounds significantly inhibited IgE production in U266 cells, with arctigenin the most potent (IC50=5.09µg/mL). Arctigenin (at a dose of 13 mg/kg) markedly reduced peanut-specific IgE levels, blocked hypothermia and histamine release in a peanut-allergic mouse model. Arctigenin also significantly reduced IgE production and Th2 cytokines (IL-5, IL-13) by PBMCs. We found 479 differentially expressed genes in PBMCs with arctigenin treatment (p < .001 and fold-change ≥1.5), involving 24 gene ontology terms (p < .001, FDR <0.05); cell division was the most significant. Eleven genes including UBE2C and BCL6 were validated by qPCR. CONCLUSION: Arctigenin markedly inhibited IgE production in U266 cells, peanut-allergic murine model and PBMCs from allergic patients by down-regulating cell division, cell cycle-related genes and up-regulating anti-inflammatory factors.

Role of hepatic PKCß in nutritional regulation of hepatic glycogen synthesis.

The signaling mechanisms by which dietary fat and cholesterol signals regulate central pathways of glucose homeostasis are not completely understood. By using a hepatocyte-specific PKCß-deficient (PKCßHep-/-) mouse model, we demonstrated the role of hepatic PKCß in slowing disposal of glucose overload by suppressing glycogenesis and increasing hepatic glucose output. PKCßHep-/- mice exhibited lower plasma glucose under the fed condition, modestly improved systemic glucose tolerance and mildly suppressed gluconeogenesis, increased hepatic glycogen accumulation and synthesis due to elevated glucokinase expression and activated glycogen synthase (GS), and suppressed glucose-6-phosphatase expression compared with controls. These events were independent of hepatic AKT/GSK-3α/ß signaling and were accompanied by increased HNF-4α transactivation, reduced FoxO1 protein abundance, and elevated expression of GS targeting protein phosphatase 1 regulatory subunit 3C in the PKCßHep-/- liver compared with controls. The above data strongly imply that hepatic PKCß deficiency causes hypoglycemia postprandially by promoting glucose phosphorylation via upregulating glucokinase and subsequently redirecting more glucose-6-phosphate to glycogen via activating GS. In summary, hepatic PKCß has a unique and essential ability to induce a coordinated response that negatively affects glycogenesis at multiple levels under physiological postprandial conditions, thereby integrating nutritional fat intake with dysregulation of glucose homeostasis.

Systems Pharmacology and In Silico Docking Analysis Uncover Association of CA2, PPARG, RXRA, and VDR with the Mechanisms Underlying the Shi Zhen Tea Formula Effect on Eczema.

Eczema is a complex chronic inflammatory skin disease impacted by environmental factors, infections, immune disorders, and deficiencies in skin barrier function. Shi Zhen Tea (SZT), derived from traditional Chinese medicine Xiao-Feng-San, has shown to be an effective integrative therapy for treating skin lesions, itching, and sleeping loss, and it facilitates reduction of topical steroid and antihistamine use in pediatric and adult patients with severe eczema. Yet, its active compounds and therapeutic mechanisms have not been elucidated. In this study, we sought to investigate the active compounds and molecular mechanisms of SZT in treating eczema using systems pharmacology and in silico docking analysis. SZT is composed of 4 medicinal herbs, Baizhu (Atractylodis macrocephalae rhizome), Jingjie (Schizonepetae herba), Kushen (Sophorae flavescentis radix), and Niubangzi (Arctii fructus). We first identified 51 active compounds from SZT and their 81 potential molecular targets by high-throughput computational analysis, from which we identified 4 major pathways including Th17 cell differentiation, metabolic pathways, pathways in cancer, and the PI3K-Akt signaling pathway. Through network analysis of the compound-target pathway, we identified hub molecular targets within these pathways including carbonic anhydrase II (CA2), peroxisome proliferator activated receptor γ (PPAR γ), retinoid X receptor α (RXRA), and vitamin D receptor (VDR). We further identified top 5 compounds including cynarine, stigmasterin, kushenol, ß-sitosterol, and (24S)-24-propylcholesta-5-ene-3ß-ol as putative key active compounds on the basis of their molecular docking scores with identified hub target proteins. Our study provides an insight into the therapeutic mechanism underlying multiscale benefits of SZT for eczema and paves the way for developing new and potentially more effective eczema therapies.

Frequent clinical and radiological manifestations of the Novel SARS-CoV-2: A review article.

Coronavirus disease 2019 (COVID-19) is a highly infectious disease caused by the novel "severe acute respiratory syndrome coronavirus-2" (SARS-CoV-2) and is rapidly spreading worldwide. This review is designed to highlight the most common clinical features and computed tomography (CT) signs of patients with COVID-19 and to elaborate the most significant signs indicative of COVID-19 diagnosis. This review involved five original articles with both clinical and radiological features of COVID-19 published during Jan and Mar 2020. In this review, the most frequent symptoms of COVID-19 were fever and cough. Myalgia, fatigue, sore throat, headache, diarrhea, and dyspnea were less common manifestations. Nausea and vomiting were rare. Ground-glass opacity (GGO) was the most common radiological finding on CT, and mixed GGO with consolidation was reported in some cases. In addition, elevated C-reactive protein and lymphopenia are the pertinent laboratory findings of COVID-19. CT is an effective and important imaging tool for both diagnosis and follow-up COVID-19 patients with varied features, duration, and course of the disease. Bilateral GGOs, especially in the periphery of the lungs with or without consolidation, are the hallmark of COVID-19.

Autoamputated pharyngeal hairy polyp presented with aero-digestive obstruction: A case report.

A pharyngeal hairy polyp (HP) is a rare benign mass that can be surgical detached with few complications. In this report, we describe a hairy polyp in a 7-day-old neonate presented with intermittent respiratory distress and feeding difficulties since birth. Neck computed tomography was performed, and demonstrated a well-defined pedunculated heterogeneous mass arising from the right lateral wall of the nasopharynx extending downward and nearly completely obstructing of the nasopharynx and oropharynx. The central part of the mass was found relatively dense surrounded by low attenuation fatty components with enhancement of the outer wall of the mass. The provisional diagnosis was pharyngeal HP. After autoamputation at the seventh day old, HP was analyzed via histopathology examination that showed a mixture of various ectodermal and mesodermal tissues including skin, cartilage, adipose and fibrous tissue. The patient fully recovered with no residual clinical features. We report this case to elucidate the possibility of this strange behavior of pharyngeal HP.

Synthesis and antibacterial study of cell-penetrating peptide conjugated trifluoroacetyl and thioacetyl lysine modified peptides.

Substrate-based sirtuin inhibitors target bacterial genome and RNA and provide a promising approach to address bacterial resistance issues, if cellular internalisation can be achieved. We designed N-trifluoroacetyl lysine and N-thioacetyl lysine peptides (KP 13, KP 15 and KP 24) as inhibitors of bacterial sirtuins and their cell-penetrating peptide conjugates Tat KP 13, Tat KP 15 and Tat KP 24. The conjugated peptides were successfully internalised and showed signs of bacterial transcription inhibition resulting in enhanced antibacterial potency against model Gram negative and Gram positive pathogens. Synergistic activity in combination with streptomycin and polymyxin B has also been established. These peptides were effective in inhibiting biofilm formation and eradicating preformed biofilms. Morphological analysis using both SEM and TEM showed bacterial membrane disruption. Calcein dye leakage analysis established the selectivity of these peptides to bacterial membranes. This study documents the first report of the application of substrate-based sirtuin inhibitors as antimicrobial therapeutics.

Microbiota-Derived Metabolites, Indole-3-aldehyde and Indole-3-acetic Acid, Differentially Modulate Innate Cytokines and Stromal Remodeling Processes Associated with Autoimmune Arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the synovial joints. Inflammation, new blood vessel formation (angiogenesis) and bone resorption (osteoclastogenesis) are three key processes involved in the joint damage and deformities of arthritis. Various gut microbiota-derived metabolites are implicated in RA pathogenesis. However, there is barely any information about the impact of two such metabolites, indole-3-aldehyde (IAld) and indole-3-acetic acid (I3AA), on arthritis-related processes. We conducted a comparative analysis of IAld and I3AA using established cell-based models to understand how they might influence RA pathogenesis. Although structurally similar, the bioactivities of these two metabolites were profoundly different. IAld but not I3AA, inhibited the expression of pro-inflammatory cytokines (IL-1ß and IL-6) in RAW 264.7 (RAW) cells stimulated with heat-killed M. tuberculosis sonicate (Mtb) and lipopolysaccharide (LPS). IAld also exhibited pro-angiogenic activity and pro-osteoclastogenic activity. In contrast, I3AA exhibited anti-angiogenic activity on endothelial cell tube formation but had no effect on osteoclastogenesis. Both IAld and I3AA have been proposed as aryl hydrocarbon receptor (AhR) agonists. Use of CH-223191, an inhibitor of the AhR, suppressed the anti-angiogenic activity of I3AA but failed to mitigate the effects of IAld. Further investigation of the anti-inflammatory activities of IAld and I3AA in LPS-treated RAW cells indicated that inhibition of MyD88-dependent activation of NF-κB and MAPK pathways was not likely involved. Our results suggest that the relative bioavailability of these indole derivatives may differentially impact RA progression and possibly other diseases that share similar cellular processes.

Comparative Analysis of Brainstem Auditory Evoked Potential Patterns between Menstruating and Menopausal North Indian Females.

Introduction: Various studies suggest a significant impact of gonadal hormones on many neuronal functions, including auditory processing. Although a few researchers have independently investigated the brainstem auditory evoked potential (BAEP) patterns during various phases of menstrual cycle and also during menopause, there is an acute paucity of comparative data between their BAEP patterns. This study was conducted to compare the BAEP patterns between normally menstruating females and menopausal females from North India. Materials and Methods: A cross-sectional study was done on 90 females aged 17-21 years who were in the follicular phase of their menstrual cycle and 100 menopausal females aged 46-70 years. BAEP recording was done using standardized protocol. The data were analyzed using SPSS software. It contained mean wave latencies I, II, III, IV, V, and Interpeak Latencies (IPL) I-V, I-III, and III-V. Results: The mean values of latencies of waves I, III, and V and also of IPL I-III, I-V, and III-V were significantly higher (P > 0.05) in menopausal females. However, the difference between mean values of wave latencies II and IV of both groups was statistically non-significant (P > 0.05). Conclusion: The increased latencies in menopausal females indicate subtle degenerative changes that start appearing within the central auditory pathway after menopause and are probably due to a decline in ovarian hormones, especially estrogen.

Hepatocyte-specific PKCß deficiency protects against high-fat diet-induced nonalcoholic hepatic steatosis.

OBJECTIVE: Nonalcoholic hepatic steatosis, also known as fatty liver, is a uniform response of the liver to hyperlipidic-hypercaloric diet intake. However, the post-ingestive signals and mechanistic processes driving hepatic steatosis are not well understood. Emerging data demonstrate that protein kinase C beta (PKCß), a lipid-sensitive kinase, plays a critical role in energy metabolism and adaptation to environmental and nutritional stimuli. Despite its powerful effect on glucose and lipid metabolism, knowledge of the physiological roles of hepatic PKCß in energy homeostasis is limited. METHODS: The floxed-PKCß and hepatocyte-specific PKCß-deficient mouse models were generated to study the in vivo role of hepatocyte PKCß on diet-induced hepatic steatosis, lipid metabolism, and mitochondrial function. RESULTS: We report that hepatocyte-specific PKCß deficiency protects mice from development of hepatic steatosis induced by high-fat diet, without affecting body weight gain. This protection is associated with attenuation of SREBP-1c transactivation and improved hepatic mitochondrial respiratory chain. Lipidomic analysis identified significant increases in the critical mitochondrial inner membrane lipid, cardiolipin, in PKCß-deficient livers compared to control. Moreover, hepatocyte PKCß deficiency had no significant effect on either hepatic or whole-body insulin sensitivity supporting dissociation between hepatic steatosis and insulin resistance. CONCLUSIONS: The above data indicate that hepatocyte PKCß is a key focus of dietary lipid perception and is essential for efficient storage of dietary lipids in liver largely through coordinating energy utilization and lipogenesis during post-prandial period. These results highlight the importance of hepatic PKCß as a drug target for obesity-associated nonalcoholic hepatic steatosis.