Olanzapine induced biochemical and histopathological changes after its chronic administration in rats

AbstractObjective: Olanzapine is a second generation antipsychotic acting mainly as a dopamine D2 and serotonine 5-HT2 receptors antagonist prescribed in the treatment of schizophrenia and various other psychiatric illnesses. Even though olanzapine is widely used in psychiatry, its effects on the architecture of pancreas, liver and kidneys are little known. The histology of pancreas especially has never been studied. For these reasons, the current study was designed to elucidate the toxic effects of chronic administration of olanzapine on pancreas, liver and kidneys and the enzymes released by these tissues in an escalating dose manner. Methods: Fourteen male rats were divided into two groups equally, the olanzapine group and the controls. Olanzapine was administered in a dose of 5mg/kg/d for the first eight weeks, 10mg/kg/d for next four weeks and 15mg/kg/d through the last two week period of 14weeks experiment. The controls received acidified saline only. Both the groups received restricted diet (20g/12h). The body weight and level of random blood sugar (RBS) were measured on a weekly basis. The levels of lipase, amylase, alanine transaminase (ALT) and aspartate transaminase (AST) were determined terminally. At the end of the experiment, the tissues were dissected out for histopathological evaluation. Results: Significant loss in body weight, change in the level of random blood sugar (∗∗P<0.05, ∗∗∗P<0.001) and significant rise in amylase and lipase levels (∗P<0.05, ∗∗∗P<0.001) were observed. However, the same treatment has shown no significant change in the levels of alanine and aspartate transaminases (P>0.05). The pancreas has shown derangement of beta cells and fibrotic growth. A mild to moderate focal increase in glomerular cellularity, cellular proliferation and glomerular capsules with negligible basement membranes were observed in the kidneys. No changes were observed in the architecture of the liver. Conclusion: The findings of this study indicated that the incidence of adverse effects associated with olanzapine could be prevented/alleviated/delayed by allowing restricted diet

Novel hydroquinone derivatives alleviate algesia, inflammation and pyrexia in the absence of gastric ulcerogenicity

Purpose: To synthesize and characterize novel hydroquinone compounds that exhibit an aspirin-like pharmacological profile devoid of ulcerogenic side effects.Methods: Two novel hydroquinone derivatives, viz, 2,5-bis(piperidinomethyl)hydroquinone and 2,5- bis(pyrrolidinomet hyl)hydroquinone, were synthesized by refluxing hydroquinone, paraformaldehyde and secondary amines (piperidine or pyrrolidine) in ethanol. The structures were authenticated by infrared (IR) spectroscopy, elemental analysis, mass spectrometry (MS) and 1H and 13C nuclear magnetic resonance (NMR) spectroscopic techniques. The synthesized derivatives were evaluated for antinociceptive, anti-inflammatory and antipyretic activities along with gastric-ulcerogenicity using wellknown testing paradigms. Aspirin served as reference standard.Results: The newly synthesized hydroquinone derivatives, significantly attenuated tonic visceral chemically-induced nociception at 10 mg/kg (p &lt; 0.01, p &lt; 0.001), 20 and 40 mg/kg (p &lt; 0.001), inhibited the temporal-inflammatory reaction at 50 mg/kg (2 - 5 h, p &lt; 0.05, p &lt; 0.001), 100 and 150 mg/kg (1 - 5 h, p &lt; 0.05, p &lt; 0.01, p &lt; 0.001) in addition to alleviating the febrile-response at test doses during 0.5 h (p &lt; 0.05, p &lt; 0.01, p &lt; 0.001), 1 and 1.5 h (p &lt; 0.001) of the study period. The synthesized compounds exhibited improved gastric tolerability profile since they were devoid of aspirin-associated biochemical and ulcerative changes. The in silico studies predicted high binding affinity of the hydroquinone derivatives to the active site of the cyclooxygenase 2 (COX-2) enzyme.Conclusion: The synthesized hydroquinone compounds possess analgesic, antipyretic and antiinflammatory properties with low gastric-ulcerogenic potential. This may be credited to preferential inhibition of the COX-2 enzyme and the beneficial basic rather than acidic chemical nature of the compounds. However, further molecular studies are required to substantiate these findings.Keywords: 2,5-Bis(piperidinomethyl)hydroquinone], 2,5- is(pyrrolidinomethyl)hydroquinone, Antiinflammatory, Antinociceptive, Antipyretic, Gastric-ulcerogenicity, Algesi

Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort

\ua9 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Individuals with rare kidney diseases account for 5–10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure. Methods: People aged 0–96 years living with 28 types of rare kidney diseases were recruited from 108 UK renal care facilities. The primary outcomes were cumulative incidence of mortality and kidney failure in individuals with rare kidney diseases, which were calculated and compared with that of unselected patients with chronic kidney disease. Cumulative incidence and Kaplan–Meier survival estimates were calculated for the following outcomes: median age at kidney failure; median age at death; time from start of dialysis to death; and time from diagnosis to estimated glomerular filtration rate (eGFR) thresholds, allowing calculation of time from last eGFR of 75 mL/min per 1\ub773 m2 or more to first eGFR of less than 30 mL/min per 1\ub773 m2 (the therapeutic trial window). Findings: Between Jan 18, 2010, and July 25, 2022, 27 285 participants were recruited to RaDaR. Median follow-up time from diagnosis was 9\ub76 years (IQR 5\ub79–16\ub77). RaDaR participants had significantly higher 5-year cumulative incidence of kidney failure than 2\ub781 million UK patients with all-cause chronic kidney disease (28% vs 1%; p&lt;0\ub70001), but better survival rates (standardised mortality ratio 0\ub742 [95% CI 0\ub732–0\ub752]; p&lt;0\ub70001). Median age at kidney failure, median age at death, time from start of dialysis to death, time from diagnosis to eGFR thresholds, and therapeutic trial window all varied substantially between rare diseases. Interpretation: Patients with rare kidney diseases differ from the general population of individuals with chronic kidney disease: they have higher 5-year rates of kidney failure but higher survival than other patients with chronic kidney disease stages 3–5, and so are over-represented in the cohort of patients requiring kidney replacement therapy. Addressing unmet therapeutic need for patients with rare kidney diseases could have a large beneficial effect on long-term kidney replacement therapy demand. Funding: RaDaR is funded by the Medical Research Council, Kidney Research UK, Kidney Care UK, and the Polycystic Kidney Disease Charity

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Passiflora incarnata attenuation of neuropathic allodynia and vulvodynia apropos GABA-ergic and opioidergic antinociceptive and behavioural mechanisms

Background: Passiflora incarnata is widely used as an anxiolytic and sedative due to its putative GABAergic properties. Passiflora incarnata L. methanolic extract (PI-ME) was evaluated in an animal model of streptozotocininduced diabetic neuropathic allodynia and vulvodynia in rats along with antinociceptive, anxiolytic and sedative activities in mice in order to examine possible underlying mechanisms. Methods: PI-ME was tested preliminary for qualitative phytochemical analysis and then quantitatively by proximate and GC-MS analysis. The antinociceptive property was evaluated using the abdominal constriction assay and hot plate test. The anxiolytic activity was performed in a stair case model and sedative activity in an open field test. The antagonistic activities were evaluated using naloxone and/or pentylenetetrazole (PTZ). PI-ME was evaluated for prospective anti-allodynic and anti-vulvodynic properties in a rat model of streptozotocin induced neuropathic pain using the static and dynamic testing paradigms of mechanical allodynia and vulvodynia. Results: GC-MS analysis revealed that PI-ME contained predominant quantities of oleamide (9-octadecenamide), palmitic acid (hexadecanoic acid) and 3-hydroxy-dodecanoic acid, among other active constituents. In the abdominal constriction assay and hot plate test, PI-ME produced dose dependant, naloxone and pentylenetetrazole reversible antinociception suggesting an involvement of opioidergic and GABAergic mechanisms. In the stair case test, PI-ME at 200 mg/kg increased the number of steps climbed while at 600 mg/kg a significant decrease was observed. The rearing incidence was diminished by PI-ME at all tested doses and in the open field test, PI-ME decreased locomotor activity to an extent that was analagous to diazepam. The effects of PI-ME were antagonized by PTZ in both the staircase and open field tests implicating GABAergic mechanisms in its anxiolytic and sedative activities. In the streptozotocin-induced neuropathic nociceptive model, PI-ME (200 and 300 mg/kg) exhibited static and dynamic anti-allodynic effects exemplified by an increase in paw withdrawal threshold and paw withdrawal latency. PI-ME relieved only the dynamic component of vulvodynia by increasing flinching response latency. Conclusions: These findings suggest that Passiflora incarnata might be useful for treating neuropathic pain. The antinociceptive and behavioural findings inferring that its activity may stem from underlying opioidergic and GABAergic mechanisms though a potential oleamide-sourced cannabimimetic involvement is also discussed

Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort

Background Individuals with rare kidney diseases account for 5–10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure. Methods People aged 0–96 years living with 28 types of rare kidney diseases were recruited from 108 UK renal care facilities. The primary outcomes were cumulative incidence of mortality and kidney failure in individuals with rare kidney diseases, which were calculated and compared with that of unselected patients with chronic kidney disease. Cumulative incidence and Kaplan–Meier survival estimates were calculated for the following outcomes: median age at kidney failure; median age at death; time from start of dialysis to death; and time from diagnosis to estimated glomerular filtration rate (eGFR) thresholds, allowing calculation of time from last eGFR of 75 mL/min per 1·73 m2 or more to first eGFR of less than 30 mL/min per 1·73 m2 (the therapeutic trial window). Findings Between Jan 18, 2010, and July 25, 2022, 27 285 participants were recruited to RaDaR. Median follow-up time from diagnosis was 9·6 years (IQR 5·9–16·7). RaDaR participants had significantly higher 5-year cumulative incidence of kidney failure than 2·81 million UK patients with all-cause chronic kidney disease (28% vs 1%; p<0·0001), but better survival rates (standardised mortality ratio 0·42 [95% CI 0·32–0·52]; p<0·0001). Median age at kidney failure, median age at death, time from start of dialysis to death, time from diagnosis to eGFR thresholds, and therapeutic trial window all varied substantially between rare diseases. Interpretation Patients with rare kidney diseases differ from the general population of individuals with chronic kidney disease: they have higher 5-year rates of kidney failure but higher survival than other patients with chronic kidney disease stages 3–5, and so are over-represented in the cohort of patients requiring kidney replacement therapy. Addressing unmet therapeutic need for patients with rare kidney diseases could have a large beneficial effect on long-term kidney replacement therapy demand. Funding RaDaR is funded by the Medical Research Council, Kidney Research UK, Kidney Care UK, and the Polycystic Kidney Disease Charity

लघुपाराशरी, अर्थात्, उडुदायप्रदीप / अनुवादक, चतुर्वेद चन्द्रशेखर शास्त्री

application/pdf'Laghuparasari'--Hindu astrology book Laguparasari, Sanskrit texts and Hindi translation / Rajajyotish

Fortifying Smart Home Security: A Robust and Efficient User-Authentication Scheme to Counter Node Capture Attacks

In smart home environments, the interaction between a remote user and devices commonly occurs through a gateway, necessitating the need for robust user authentication. Despite numerous state-of-the-art user-authentication schemes proposed over the years, these schemes still suffer from security vulnerabilities exploited by the attackers. One severe physical attack is the node capture attack, which allows adversaries to compromise the security of the entire scheme. This research paper advances the state of the art by conducting a security analysis of user-authentication approaches regarding their vulnerability to node capture attacks resulting in revelations of several security weaknesses. To this end, we propose a secure user-authentication scheme to counter node capture attacks in smart home environments. To validate the effectiveness of our proposed scheme, we employ the BAN logic and ProVerif tool for verification. Lastly, we conduct performance analysis to validate the lightweight nature of our user-authentication scheme, making it suitable for IoT-based smart home environments

مثنوی تصویر جاناں / تصنیف لچهمی ناراین شفیق اورنگ آبادی ; مرتبہ, حمیدالدین شاہد

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Enhancing Security and Privacy in Healthcare Systems Using a Lightweight RFID Protocol

Exploiting Radio Frequency Identification (RFID) technology in healthcare systems has become a common practice, as it ensures better patient care and safety. However, these systems are prone to security vulnerabilities that can jeopardize patient privacy and the secure management of patient credentials. This paper aims to advance state-of-the-art approaches by developing more secure and private RFID-based healthcare systems. More specifically, we propose a lightweight RFID protocol that safeguards patients’ privacy in the Internet of Healthcare Things (IoHT) domain by utilizing pseudonyms instead of real IDs, thereby ensuring secure communication between tags and readers. The proposed protocol has undergone rigorous testing and has been proven to be secure against various security attacks. This article provides a comprehensive overview of how RFID technology is used in healthcare systems and benchmarks the challenges faced by these systems. Then, it reviews the existing RFID authentication protocols proposed for IoT-based healthcare systems in terms of their strengths, challenges, and limitations. To overcome the limitations of existing approaches, we proposed a protocol that addresses the anonymity and traceability issues in existing schemes. Furthermore, we demonstrated that our proposed protocol had a lower computational cost than existing protocols and ensured better security. Finally, our proposed lightweight RFID protocol ensured strong security against known attacks and protected patient privacy using pseudonyms instead of real IDs