International journal of physiology, pathophysiology and pharmacology最新文献

Backgrounds: Impaired sleep is independent risk factor of neurodegeneration and dementia. Chronic insomnia impairs melatonin (MEL) production that is directly proportionate to its duration. The underlying mechanisms linking sleep loss to dementia and the possible therapeutic effect of melatonin have not been fully elucidated. Previous research showed great controversy concerning the effects of paradoxical sleep deprivation (PSD) on body weight, serum lipoproteins, and inflammatory cytokines.

Goals: To examine the effect of chronic paradoxical sleep deprivation (PSD) with and without MEL supplementation on memory using RAWM, parameters of metabolic syndrome (MS), liver enzymes, serum cortisol, and inflammatory cytokines as well as liver, colon, and brain histopathology.

Methods: Forty rats were divided into four groups ten animals each; C: control, G: grid group, SD: sleep deprivation group, and SD+MEL sleep deprivation treated with melatonin.

Results: MEL supplementation reversed PSD-induced memory deficits (P<0.05), the elevation of serum cortisol (P<0.001), glucose (P<0.05), ALT (P<0.05), AST (P<0.001), TNF-alpha (P<0.001), IL-10 (P<0.01) and improved colon, liver, and brain architecture. Melatonin reduced body weight (P<0.05), total cholesterol, LDL-c, and triglycerides as well as increased HDL-c (P<0.001).

Conclusion: MEL has a protective effect against chronic PSD-induced metabolic malfunction and cognitive deterioration by reducing stress, improving immunity, and maintaining colonic wall integrity.

Objective: To explore the effect of Shenqi millet porridge on treating gastrointestinal function decline.

Methods: Clinical data of 72 patients with gastrointestinal function decline were retrospectively analyzed. Patients were divided into an observation group (n=36, treated with Shenqi millet porridge) and a control group (n=36, treated with Changweikang granule) according to the treatment methods. The therapeutic effect, quality of life, nutritional status, and levels of motilin and gastrin were analyzed.

Results: The total response rate of the observation group was significantly higher than that of the control group (97.22% vs. 72.22%; P<0.05). Compared with the control group, the quality of life in the observation group was increased after treatment (all P<0.05), and the total protein and body mass index in the observation group were higher than those in the control group (all P<0.05), while the levels of motilin and gastrin in the observation group were lower than those in the control group (all P<0.05).

Conclusion: For patients with gastrointestinal function decline, the therapeutic regimen Shenqi millet porridge ameliorates the nutritional status of patients, as well as the quality of life and total therapeutic efficacy, also reduces the levels of motilin and gastrin. This regimen has high safety and clinical application value.

Objectives: To assess the effect of isotonic normal saline (NS) versus water post-Ryles Tube (RT) feeding upon hyponatremia and blood parameters in Intensive Care Units (ICU) admitted patients.

Methods: A parallel group randomized controlled trial design. The total sample size taken for this pilot trial was N = 50 as a thumb rule (n = 25 in each arm) selected by using a simple random sampling method. The sample was ICU-admitted patients with mild and moderate hyponatremia.at tertiary care hospital, Rishikesh. Intervention-20 mL Isotonic 0.9% normal saline (NS) among the experimental group vs. 20 mL water in the control group after each 9 am Ryles tube feeding respectively for three continuous days. At baseline and follow-up electrolytes, blood parameters, Glasgow Coma Scale (GCS), and blood pressures were assessed post-one hour of intervention daily for day-1, 2, 3 & 5. Data were analyzed by using descriptive & inferential statistics in the SPSS software 23.0 version.

Results: There was a significant difference found between the experimental and control groups for the post-test value of serum sodium levels, GCS, Systolic Blood Pressure, and Diastolic Blood Pressure (DBP) at day 1 of administration of normal saline intervention with p-value < 0.0001. However, it was found significant at day 5 between both groups for the above-mentioned variables.

Conclusion: The intervention of normal saline was found to be a cheaper and more effective remedy to treat hyponatremia and reduce mortality among ICU-admitted patients due to deterioration in bio-physiological parameters.

Despite the introduction of combined antiretroviral therapy (cART) HIV-1 virus persists in the brain in a latent or restricted manner and viral proteins, such as gp120, continue to play a significant disease-inciting role. Gp120 is known to interact with N-methyl-D-aspartate (NMDA) receptors (NMDARs) resulting in neuronal injury. Glutamate is the main excitatory neurotransmitter in the brain and plays an important role in cognitive function and dysregulation of excitatory synaptic transmission impairs neurocognition. It is our hypothesis that gp120 may alter synaptic function via modulating glutamate function from a physiological molecule to a pathophysiological substance. To test this hypothesis, we studied the modulatory effects of gp120 and glutamate on NMDAR-mediated spontaneous excitatory postsynaptic current (sEPSC_NMDAR) and dynamic dendritic spine changes in rat cortical neuronal cultures. Our results revealed that gp120 and glutamate each, at low concentrations, had no significant effects on sEPSC_NMDAR and dendritic spines, but increased sEPSC_NMDAR frequency, decreased numbers of dendritic spines when tested in combination. The observed effects were blocked by either a CXCR4 blocker or an NMDAR antagonist, indicating the involvements of chemokine receptor CXCR4 and NMDARs in gp120 modulation of glutamate effects. These results may imply a potential mechanism for HIV-1-associated neuropathogenesis in the cART era.

Background: Paracetamol (acetaminophen) is an over-the-counter non-steroidal anti-inflammatory drug that may cause acute toxic overdosage particularly in neuropsychiatric patients. Paracetamol is also very commonly prescribed as an analgesic and antipyretic agent. Paracetamol toxicity causes decreased reduced glutathione and oxidative tissue damage. Aleppo galls is a promising natural remedy exerting antioxidant and tissue-protective effects that may combat acetaminophen-induced oxidative tissue damage.

Methodology: Biochemical and toxicological effects of a toxic dose of paracetamol (250 mg/kg) were investigated for three consecutive days versus the tissue-protective effects of Aleppo galls. Eighteen white albino mice were randomly allocated in this study and divided into three experimental groups (six mice per group): negative control (received intraperitoneal sterile water injection), paracetamol toxicity group (received intraperitoneal paracetamol injection) and the third group (received paracetamol injection at 250 mg/kg/day together with oral Aleppo galls treatment at 250 mg/kg/day for 3 consecutive days). All mice were sacrificed by the end of the study.

Results: Our data revealed that paracetamol toxicity exerted significant oxidative stress damaging effects (high serum malondialdehyde, decreased serum catalase and decreased total antioxidant capacity), and significant inflammatory effects (high serum IL-6) and significant tissue-damaging effects (high serum LDH). Aleppo galls treatment significantly protected against acetaminophen toxicity-induced oxidative stress effects (P<0.001), inflammatory effects (P<0.001) and tissue-damaging effects (P<0.001).

Conclusion: Aleppo galls are promising for future drug therapeutics and for the synthesis of natural remedies for treating paracetamol toxicity. We recommend formulating Aleppo galls extract as a pharmaceutical nutrition and to be given to those who need to take large doses of paracetamol.

Objectives: The goal of this study was to evaluate a low fixed-dose versus weight-based dosing strategy for four-factor prothrombin complex (4F-PCC) time to administration in intracranial hemorrhage (ICH) patients.

Methods: A retrospective analysis was conducted at a single rural Tertiary referral center in patients ≥18 years old on warfarin with ICH who received 4F-PCC. Continuous variables were summarized using mean (±95% CI) and compared using two-tailed tests; p values ≤0.05 were considered statistically significant.

Results: A total of 46 ICH patients were reversed using 4F-PCC (Fixed, n = 27 and Weight, n = 19). Baseline characteristics were equivalent. Total units of 4F-PCC (mean dose units 2525.1 versus 1623.3) and dose per kg were significantly reduced in the fixed-dose group. Total time from order to delivery was significantly reduced with the fixed-dose strategy (mean time 43.0 versus 29.0 minutes). Hospital length of stay (LOS), intensive care unit LOS, and mortality were equivalent with a similar mechanism. International Normalized Ratio (INR) reversal success (≤1.5) and total INR change was comparable with no difference in adverse thromboses between groups.

Conclusions: A fixed-dosed strategy reduced time to 4F-PCC administration for warfarin reversal in ICH, as compared to a weight-based strategy; with no increase in LOS, mortality, or need for additional dosing. This also resulted in significant cost savings.

Background and objective: Lysine is an essential amino acid involved in several biochemical pathways. It has been shown to enhance blood supply and target growth factors, leading to improved wound healing. The present study aimed to evaluate the efficacy and tolerability of a 15% lysine cream in treating diabetic foot ulcers, as measured by the Bates-Jensen Wound Assessment Tool (BWAT).

Materials and method: A randomized, open-label, interventional study was conducted on 40 volunteers with diabetic ulcers. The treatment group (n=20) received well-known treatment along with lysine cream (15%) twice daily, while the control group (n=20) received standard therapy alone. Wound healing was evaluated using the BWAT. The student t-test and one-way ANOVA were used to compare the clinical assessment parameters to the baseline.

Results: Both groups showed a significant decrease in ulcer size, depth, edges, undermining, necrotic tissue type, necrotic tissue amount, exudate type, and exudate amount over six weeks, with no significant difference between the groups after the first week. The lysine-treated group showed a significant improvement in wound healing compared to the control group (P<0.05).

Conclusion: The present study demonstrates that a 15% lysine cream can significantly improve wound healing in diabetic foot ulcer patients, as measured by the BWAT, compared to standard treatment alone. Further research is needed to confirm these findings and to explore the underlying mechanisms of lysine's therapeutic effects.

Ultraviolet (UV) radiation is a major cause of multiple major skin diseases including skin cancer. It is crucial to discover new agents that can produce profound protective effects on UV-produced skin damage. Using a mouse model, in this study we determined the effects of NAD⁺ on UVC-induced skin damage and investigated the mechanisms underlying the effects, obtaining the following discoveries: First, UVC-induced skin's green autofluorescence (AF) was highly correlated with the extent of UVC-indued skin's damage; second, NAD⁺ administration profoundly decreased UVC-induced skin damage; third, NAD⁺ administration significantly attenuated UVC-induced decreases in the levels of mitochondrial superoxide dismutase and catalase; fourth, NAD⁺ administration significantly attenuated UVC-induced increase in the level of cyclooxygenase (COX) 2 - a marker of inflammation; fifth, NAD⁺ administration profoundly attenuated UVC-induced increase in double-strand DNA (dsDNA) damage; and sixth, NAD⁺ administration profoundly attenuated UVC-induced decreases in the ratios of Bcl-2/Bax - an index of apoptosis. Collectively, our study has found that NAD⁺ administration can profoundly decrease UVC-induced skin damage by attenuating oxidative stress, inflammation, DNA damage, and apoptosis, suggesting great potential of NAD⁺ as a protective agent for UVC-induced skin damage. Moreover, our study has further indicated that the skin's green AF is a biomarker for predicting UVC-induced skin damage.

Introduction: The cardiovascular autonomic functions can be tested by a Battery of five tests developed by Ewing and Clark in 1981 in Edinburgh. Yogic practices are immensely useful for physical, mental and spiritual development required for better autonomic function.

Aim and objectives: To assess the ANS (Autonomic function system) function with help of Ewing's Battery tests in yoga participants and healthy participants not practicing yoga.

Materials and methods: A cross-sectional study was conducted on 270 participants which were divided into two groups viz: 135 in healthy control (Group I) and 135 in yoga group (Group II). Subjects with informed consent between 40-50 years, were included in control (Group I) and those practicing yoga for past minimum 3 months were included in Group II. Anthropometric measurements were done and parasympathetic tests like Heart rate (HR) response to standing from the supine posture, to Valsalva maneuvers and to slow deep breathing were done. Also, sympathetic tests, Blood Pressure (BP) response to cold in cold pressor test (CPT), to sustained handgrip test and to standing from lying posture were carried out.

Results: P value was found to be statically significant among yoga group as compared with healthy control group in all the sympathetic and parasympathetic tests except in CPT. As per the Ewing's criteria, normal, early, diseased and severe CAN (Cardiac autonomic neuropathy) in healthy controls findings were 11.11%, 58.51%, 37.03%, 17.77% and in yoga participants findings were 37.7%, 34.8%, 6.66% and 8.88% respectively. According to Bellavere's classification, maximum diseased CAN were found in healthy control as compared to yoga group. As per AIIMS (All India Institute of Medical Sciences) criteria, parasympathetic neuropathy was observed in 11.85% of the healthy controls and in 6.66% of the yoga group, and that maximum sympathetic neuropathy was observed in 11.11% of the healthy patients and only 3.7% of the yoga group.

Conclusion: More emphasis should be given on implementation of yoga from early ages at the institutional levels, hospital levels. Yoga practices will suffice and lead to improvement of unhealthy ANS condition. Overall, Yoga showed better ANS function than healthy control group.

Background: Markers related to the mechanism of tumoral cell escape from the immune system have received more attention. The PD-L1 molecule encoded by the "CD274" gene binds to T lymphocytes and can inhibit these cells. Therefore, increasing the expression of this marker on inflammatory or tumor cells can indicate tumor progression invasiveness and long-term consequences. The present study aimed to determine the expression of the PD-L1 marker in thyroid medullary tumors and to evaluate its role in predicting long-term outcomes after cancer.

Methods: This retrospective longitudinal study was performed on pathology samples of patients with medullary thyroid carcinoma referred to the Cancer Institute of Imam Khomeini Hospital from 2015 to 2020. Slides related to medullary thyroid tumors were examined. A tissue microarray was used to evaluate the immunohistochemistry of PD-L1. Patients were followed up to assess the occurrence of recurrence. Out of 207 patients evaluated in the present study, histopathological information of 144 patients was available.

Results: The expression rate of PD-L1 in our community was 14.6% in lymphocyte cells, 35.4% in tumor cells, and 12.5% in both cells. The presence of metastasis at the time of diagnosis was reported in 35 cases (72.9%), and the occurrence of tumor recurrence was reported in 38 cases (79.2%). There was no relationship between the expression of this marker and the sex and age of patients. In addition, PD-L1 expression was unrelated to the two main characteristics of this cancer, namely tumor size and its focality. The presentation of tumor PD (L1) (but not lymphocytic) was a prognostic marker for synchronous metastasis at cancer diagnosis but could not predict tumor recurrence.

Conclusion: PD-L1 tumor marker expression is predictable in 14.6% of lymphocyte cells, 35.4% of tumor cells, and 12.5% in the selected Iranian population with medullary thyroid cancer. The expression of this marker is not related to the morphological characteristics of the tumor, such as tumor size or focality.