Hyponatremia is one of the most common electrolyte disorders in clinical practice and is frequently observed following thiazide use. Advanced age and female gender are implicated in the etiology of hydrochlorothiazide (HCTZ)-associated hyponatremia. There has also recently been mention of a genetic disposition. This study evaluated the genetic component, and particularly the clinical significance, of variants in the SLC12A3 gene in the development of hyponatremia in hypertensive patients using HCTZ-group diuretics.

Ninety-five patients presenting to the Tekirdağ Namık Kemal University nephrology clinic and receiving antihypertensive therapy including HCTZ for at least one month were examined. Peripheral blood specimens were collected from hyponatremic (n = 62) and non-hyponatremic (n = 33) individuals. Variants in the SLC12A3 gene were analyzed using next generation sequencing and were compared with the clinical data.

A total of 947 variants were detected in the SLC12A3 gene, the majority of which were classified as of uncertain significance. Hyponatremia was determined at a higher rate in patients with c.506-276A>G (75.00%), c.282+492G>A (85.70%), c.282+499G>C (87.00%), c.282+495G>A (85.00%), and c.505+375G>A (92.30%) variants in particular. The risk of hyponatremia development increased 9.2-fold in the presence of the c.282+492G>A variant (OR = 9.243; 95% CI: 2.259-37.818; p = 0.002).

In conclusion, we think that HCTZ-associated hyponatremia cannot be predicted by clinical and biochemical parameters alone, and that genetic factors should also be considered. Further multi-center prospective studies involving larger populations will clarify the clinical significance of variants in SLC12A3 and other genes and will make a significant contribution to individualized therapeutic approaches.

Aluminum phosphide (AlP) is a chemical compound that is used as a pesticide for suicidal purposes and can cause death, and it poses a challenge to health in some countries. AlP in the presence of stomach acid leads to the release of phosphine, which inhibits mitochondrial function and reduces ATP levels. This poisoning has devastating effects on the front line of damage on the cardiovascular and gastrointestinal systems, causing symptoms such as vomiting, cardiac arrhythmias, and heart failure.A focused search was performed utilizing the terms "aluminum phosphide," "phosphine," "antidote," "case report," and "treatment" within the scientific databases Scopus, Web of Science, and PubMed. Studies have shown that supportive treatment, decontamination, and antioxidant therapy can help reduce toxic effects.Many studies have been conducted in vitro and in clinical models to identify specific antidotes, providing valuable insight into the management of poisoning. Given the lack of a particular antidote, new therapeutic approaches offer promising solutions for managing this poisoning.New knowledge, including artificial intelligence, can help prevent and manage diseases and treatments. However, further efforts are needed to develop more effective treatments and prevent the misuse of this substance.

To compare the effects of captopril and losartan on inflammatory response, angiogenesis, and fibroblast activity during the early phase of wound healing in hypertensive rats.

Twenty-seven paraffin-embedded skin wound samples from hypertensive rats were analyzed: control group (n = 8), losartan-treated group (n = 9), and captopril-treated group (n = 10). Histological and immunohistochemical analyses were performed on postoperative day 4. Hematoxylin-eosin staining was used to evaluate general wound structure, and immunohistochemistry with anti-leukocyte common antigen, anti-CD34, and anti-smooth muscle actin was performed to assess inflammatory cells, angiogenesis, and fibroblast activity, respectively.

No significant differences were observed in angiogenesis (p > 0.05) or fibroblast number (p > 0.05) between groups. However, the inflammatory reaction was significantly higher in captopril-treated (p = 0.0459) and losartan-treated (p = 0.0452) groups compared with the control group, with no significant difference between the two treated groups.

Neither captopril nor losartan influenced angiogenesis or fibroblast proliferation in the early healing phase. However, both drugs increased inflammatory cell infiltration.

Glutathione-S-transferases (GSTs) play an important role in the detoxification and neutralization of oxidative stress products and xenobiotic compounds. Due to genetic polymorphisms in GST genes, GSTs partially or completely lose enzymatic activity, which may increase susceptibility to cardiovascular diseases. The objective of this study was to investigate hitherto unknown GSTM1 and GSTT1 null genotype frequencies in patients with coronary artery disease (CAD) and their potential association with CAD in the Bangladeshi population.

This study included 85 patients with CAD and 56 healthy control subjects confirmed by angiogram. Clinical parameters including triglyceride (TG), cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein levels were also evaluated. Genotypes of the GSTM1 and GSTT1 genes were identified using polymerase chain reaction followed by 1.5% (W/V) agarose gel electrophoresis with subsequent detection on a UV transilluminator.

There were significant differences in the null genotype distribution of GSTM1 and GSTT1 alleles between controls and patients with CAD. A significant association of the null genotype with CAD susceptibility (p < 0.05) was also observed. The combination of GSTM1 and GSTT1 null genes potentially increases the risk of CAD (odds ratio = 6.208; 95% confidence interval; p < 0.05). TG, LDL, and serum cholesterol levels were higher in patients with CAD (p < 0.05). GSTM1 and GSTT1 null genetic variations may be associated with increased susceptibility to CAD in the Bangladeshi population.

These findings suggest a potential association between GST gene polymorphisms and CAD susceptibility; however, larger studies are required to provide more robust and generalizable evidence in the Bangladeshi population.

Background: Systemic arterial hypertension (SAH) induced by Nω-nitro-L-arginine methyl ester (L-NAME) is a well-established model characterized by nitric oxide (NO^●) synthase inhibition and vascular dysfunction. The transient receptor potential vanilloid 1 (TRPV1) regulates Ca²⁺ flux and may contribute to mitochondrial homeostasis. We hypothesized that TRPV1 activation modulates mitochondria function and attenuates cardiac damage during SAH. Methods: Hypertension was induced in Wistar rats by administration of L-NAME (200 mg/L) for 40 days. During the last four days, hypertensive animals received capsaicin (5 mg/kg/day), capsazepine (6 mg/kg/day), or their combination. Cardiac function was evaluated in isolated hearts using the Langendorff perfusion system. Myocardial tissue viability was assessed by triphenyltetrazolium chloride (TTC) staining, and mitochondrial function was evaluated by measuring respiratory control and apoptosis-related proteins. Results: Capsaicin treatment was associated with significant cardioprotective effects in hypertensive rats. Although the findings are consistent with a role of TRPV1 activation in mediating these effects, the partial protection observed with capsazepine suggests that TRPV1-independent mechanisms may also contribute. Conclusions: TRPV1 activation contributes to cardioprotection in SAH, likely through preservation of mitochondrial function and redox balance. However, additional mechanisms beyond TRPV1 modulation may also participate in the observed protective effects. Further studies-including direct assessment of mitochondrial Ca²⁺ flux and the use of more selective or genetic approaches-are currently underway to clarify the underlying mechanisms.

Computed tomography (CT) scan is a widely used, non-invasive, sensor-based imaging technique that provides critical intracranial information for rapid stroke assessment. Accurate segmentation of intracerebral hemorrhage (ICH) in sensor-derived CT images is vital for clinical decision-making. Effective intelligent analysis of CT images is key to achieving reliable computer-aided diagnosis. However, existing deep learning methods struggle with complex ICH lesions characterized by blurred boundaries, irregular shapes, and large-scale variations. To address these challenges, this paper proposes TransAMGNet, a hybrid U-shaped network with Transformer integration for ICH CT image segmentation. The network is built on a residual U-Net backbone and introduces a Transformer encoder to strengthen global context modeling, thereby improving the representation of complex lesion morphology. Specifically, in the encoding stage, we design an Adaptive Dual-branch Channel Attention Module (ADCAM), which jointly models global and local channel information to enhance the model's sensitivity to important feature responses. In the skip-connection pathway, we introduce a Multi-scale Feature Enhancement Module (MFEM), which preserves high-resolution spatial details while supplementing multi-scale contextual information to improve shallow-deep feature fusion. During decoding, a Gate-enhanced Dynamic Upsampling Module (GDUM) is constructed to improve the recovery of lesion boundaries and fine-grained structures through the synergy of gated recalibration and content-aware upsampling. The proposed method is systematically evaluated through comparative experiments and ablation studies. Experimental results show that TransAMGNet outperforms competing methods across multiple evaluation metrics, achieving Dice, Recall, IoU, Precision, and HD95 values of 90.47 ± 0.58%, 87.83 ± 3.71%, 81.26 ± 0.78%, 91.13 ± 0.95%, and 32.94 ± 1.1, respectively. The ablation studies further verify the effectiveness of each module. These results demonstrate that TransAMGNet can effectively improve segmentation performance for complex ICH lesions.

Alterations of gut microbiota are common in chronic kidney disease (CKD) and contribute to increased uremic toxins including indoxyl sulfate (IS), p-cresyl sulfate (pCS) and trimethylamine N-oxide (TMAO), which are linked to cerebrovascular disease risk. This study examined the kidney-gut-brain axis in CKD mice and in dialysis patients. Male and female mice with adenine-induced CKD were fed a high-amino-acid (HAA) diet to increase precursors of gut-derived uremic toxins. A subgroup of mice received antibiotics in drinking water to suppress gut microbiota and evaluate its role in toxin generation. Behavior tests, gut microbiome composition and brain histology for cerebral microhemorrhages were analyzed. CKD mice had higher serum levels of creatinine, cystatin C and gut-derived toxins, a 2.5-fold increase in brain microhemorrhages, and decreased locomotor activity. The HAA diet significantly increased serum TMAO but not IS and pCS, and all three toxins were reduced by antibiotic therapy. Sex differences were observed; in male animals, higher TMAO was associated with increased brain microhemorrhages, whereas in female mice, pCS was associated with brain microhemorrhage burden. The suppression of toxins with antibiotics improved working memory in male animals. Gut microbiota analysis revealed the expansion of Lactobacillus and Ileibacterium in CKD mice. The HAA diet and antibiotics altered gut microbiota composition without changing alpha diversity. The human study utilized biobanked serum samples and a retrospective review of brain imaging scans in a hemodialysis patient cohort; TMAO levels were associated with increased lobar microbleeds. Our study supports a role for bacterial-derived uremic toxins in the kidney-gut-brain axis and cerebral microhemorrhage formation in CKD.

Proton pump inhibitors (PPIs) are widely prescribed for acid-related disorders and are generally considered safe for short-term use. However, increasing experimental and clinical evidence suggests potential cardiovascular effects associated with chronic exposure, possibly related to endothelial dysfunction and impaired nitric oxide bioavailability. Therefore, we decided to investigate whether the cardiovascular effects of omeprazole are dependent on the timing of administration in a model of cardiac ischemia-reperfusion (CIR) in normotensive Wistar rats (NWR) and spontaneously hypertensive rats (SHR). Twelve- to sixteen-week-old male NWR and SHR were allocated into four groups: (1) SHAM: NWR and SHR were submitted to surgery with no ischemia; (2) (SS + CIR): NWR and SHR were treated with a 0.9% saline solution and submitted to CIR; and (3) (OME + ISQ): NWR and SHR were treated with 10 mg/kg i.v. omeprazole (OME) before cardiac ischemia and submitted to CIR or (4) after cardiac ischemia but before cardiac reperfusion (ISQ + OME). Electrocardiograms were monitored to assess ventricular arrhythmias (VA), atrioventricular block (AVB), and lethality (LET). Serum creatine kinase-MB (CK-MB) levels were quantified, and histopathological analyses were performed to evaluate the degree of myocardial injury in the different study groups. Administration of OME prior to cardiac ischemia increased the incidence of VA, AVB, LET, and serum CK-MB levels in both NWR and SHR. In contrast, administration before cardiac reperfusion did not exacerbate cardiac injury and was associated with the attenuation of electrophysiological instability. Histopathological findings corroborated the biochemical and functional outcomes. OME, when administered prior to cardiac ischemia, worsens both cardiac arrhythmias and myocardial injury; however, administration immediately prior to cardiac reperfusion does not increase cardiac arrhythmias and decreases myocardial injury in both NWR and SHR.

Exploration of the gene-level changes that occur during post-ischemic neurodegeneration in the frontal cortex is crucial for understanding the development of dementia. An ischemic model of Alzheimer's disease was used to evaluate changes in the expression of the receptor for advanced glycation end products (RAGE) and low-density lipoprotein receptor-related protein 1 (LRP1), which are associated with amyloid and tau protein, in the frontal cortex after 10 min of cerebral ischemia, with survival at 2, 7, and 30 days and 0.5, 1, 1.5, and 2 years. LRP1 and RAGE expression was assessed by reverse transcription-quantitative polymerase chain reaction. After two days and 1.5 and 2 years post-ischemia, LRP1 expression was increased, after 7 days and 0.5 years it was decreased, and after 30 days and 1 year it oscillated around control values. The decrease in RAGE expression was statistically significant compared to the control group after 2 and 7 days and after 0.5 years, and after 30 days it oscillated around the control value, while after 1-2 years it increased significantly. RAGE and LRP1 expression showed the same pattern of changes from day 7 to year 2, peaking at 1 and 1.5 years, respectively. Another peak of RAGE overexpression was noted 2 years after ischemia. After 1, 1.5 and 2 years, overexpression of RAGE and LRP1 was observed after ischemia, with the dynamics of LRP1 changes being lower. Overall, the data showed a predominance of RAGE expression over LRP1 expression at 1-, 1.5-, and 2-years post-ischemia. The modification of LRP1 and RAGE after ischemia is useful in studying the molecular ischemic pathways involved in the development of Alzheimer's disease.