Dysregulated miRNA-375, IL-17, TGF-ß, and Microminerals Are Associated with Calpain-10 SNP 19 in Diabetic Patients: Correlation with Diabetic Nephropathy Stages.

Zinc (Zn) and copper (Cu) have been shown to have the potential to improve glucose metabolism through interactions with cytokines and signaling events with multiple genes. miRNA-375 and the Calpin-10 gene are potential genetic biomarkers for the early prediction of diabetic nephropathy (DN). 128 healthy controls and 129 type 2 diabetic (T2DM) participants were matched for age and sex. Three subgroups were identified from the T2DM group: 39 patients had microalbuminuria, 41 had macroalbuminuria, and 49 patients had renal problems. Circulating miR-375 expression levels were measured via qPCR. Calpain-10 SNP 19 (rs3842570) genotyping was assessed with allele-specific PCR in all the included participants. Spectrophotometry was used to measure the concentrations of serum copper, zinc, and magnesium, while ELISA was used to measure the levels of TGF-ß and IL-17. There was significant up-regulation in the expression of miR-375 and serum levels of TGF-ß, IL-17, Cu, and the Cu/Zn ratio, whereas, in contrast to the control group, the Zn and Mg levels were lower in the T2DM group. The DN groups had significantly lower miR-375, TGF-ß, IL-17, Mg, and Zn levels compared with the T2DM without nephropathy group. Furthermore, between TGF-ß, IL-17, and miRNA-375, there were notable correlations. Calpain-10 SNP 19 genotype 22 and allele 2 were linked to a higher incidence of T2DM and DN. Significant TGF-ß, Cu, Cu/Zn ratio, HbAc1, and creatinine levels, but insignificant miRNA-375 levels, were associated with genotype 22 of Calpain-10 SNP 19. interactions between the Calpain-10 SNP 19 genotype 22 and IL-17, TGF-ß, mineral levels, and miRNA-375 might contribute to the aetiology of DN and T2DM and may have clinical implications for diagnosis and management.

Add dexmedetomidine to levobupivacaine for transversus abdominis plane block in elderly patients undergoing inguinal hernia repair: Could it make a difference? A randomised trial.

BACKGROUND: Transversus abdominis plane block is becoming more common as part of multimodal analgesia for post-abdominal operation pain relief. This study compared the analgesic effects of adding dexmedetomidine to levobupivacaine (transversus abdominis plane) block in elderly patients undergoing inguinal hernia surgery to adding fentanyl. METHODS: Overall, 90 elderly patients with a simple inguinal hernia repair were randomly assigned to one of three groups. After spinal anaesthesia, an ultrasound-guided transversus abdominis plane block was performed. Transversus abdominis plane block was accomplished with 0.25% levobupivacaine + 0.9% normal saline in Group L (n = 30) (20mL). Transversus abdominis plane block was accomplished with 0.25% levobupivacaine + 1 µg/kg dexmedetomidine in Group D (n = 30) (20mL). Transversus abdominis plane block was obtained with 0.25% levobupivacaine + 1 µg/kg fentanyl in Group F (n = 30) (20mL). The primary outcome was the first analgesic request, and the secondary outcomes were the visual analog scale, postoperative analgesic requirements, sedation, hemodynamic stability, and related complications 24 hours postoperatively. 1gm paracetamol intravenously was provided as rescue analgesia. RESULTS: The time to first analgesic request in the dexmedetomidine group was substantially more prolonged than in the fentanyl and control groups (516.5±27.8, 451.2±11.1, and 403.9±10.5min, respectively; p < 0.05). Postoperative analgesic requirements were significantly decreased in dexmedetomidine 1(1-2) than control 2(1-3) and fentanyl 1.5(1-2) respectively (P<0.01). VAS was significantly lower in Group D and Group F than in Group L postoperatively. No significant difference in side effects was noted between the groups. CONCLUSION: The transversus abdominis plane block is the best multimodal analgesia choice for inguinal hernia repair in older patients. Combining dexmedetomidine with levobupivacaine in the transversus abdominis plane block can improve the quality of postoperative analgesia while avoiding significant side effects.

Maternal urinary vascular endothelial growth factor (VEGF) versus N.T. pro brain natriuretic peptide (NT-pro BNP) as novel biomarkers for placental accreta spectrum (PAS): A case-control study.

This study planned to compare the predictive ability of maternal urinary vascular endothelial growth factor (VEGF) versus N-terminal pro B-type natriuretic peptide (NT-pro BNP) for prediction of placenta accreta spectrum (PAS). This was a prospective case-control study carried out in a tertiary university hospital. It included pregnant women between 37-39 weeks. The study included 50 pregnant women classified in two groups. Group (Ι, n=25) were pregnant women with PAS, and group (II, n=25) women with uncomplicated pregnancies, as controls. Urine samples were collected, and quantitative analyses of VEGF and NT-pro BNP were performed by ELISA. VEGF was assessed with a cut point of 215.6 pg/ml and NT-pro BNP with a cut point of 182.2 pg/ml to predict the condition of PAS. Both biomarkers were good predictors of PAS with the area under the ROC curve (AUC) equal to (0.871 and 0.904), respectively. However, maternal urinary VEGF levels could predict PAS better than NT-pro BNP (OR=9.967, 95%CI 2.032-48.879, p=0.005) versus (OR=8.066, 95% CI 1.520 - 42.811, p=0.014) in NT-pro BNP. In conclusion, third trimester urinary levels of both VEGF and NT-pro BNP appear to be s crucially good predictors for PAS. However, VEGF is superior to NT-pro BNP in predicting women with PAS. These biomarkers present promising candidates as they can help to detect patients at high probability of PAS. They can be assessed by non-invasive, simple, and low-cost procedures.

Antioxidant, antiapoptotic, and antifibrotic abilities of L-Arginine ameliorate the testicular dysfunction in diabetic rats.

Testicular dysfunction and infertility are serious complications of diabetes mellitus (DM). L-Arginine (L-Arg) is a semi essential amino acid with various biological and metabolic functions. The molecular mechanisms of L-Arg on testicular dysfunction caused by DM remain elusive. This study aimed to assess the potential protective effect of L-Arg in diabetic testis and its possible mechanisms. 24 adult male Wistar albino rats were randomly divided into four groups: CON, L-Arg that received 1 g/kg body weight of L-Arg orally for 4 weeks, DM that fed a high fat diet followed by an injection of 30 mg/kg streptozotocin intraperitoneally, and L-Arg-treated DM that were diabetic and administered L-Arg. DM decreased relative testicular weight, reduced serum testosterone, and impaired semen parameters. Reduced total antioxidant capacity (TAC), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px), in addition to increased transforming growth factor B1 (TGF-ß1) and nitric oxide (NO) levels, were found in the testicular tissue. This was associated with severe degenerative changes in the seminiferous tubules and interstitial cells of Leydig, reduction of Johnsen's score, significantly increased expression of both inducible nitric oxide synthase (iNOS) and caspase-3, and reduced zonula occludens (ZO)- 1 expression. Ultrastructurally, disrupted intercellular junctions and degeneration of interstitial cells of Leydig were observed. In contrast, treatment of diabetic animals with L-Arg increased TAC, SOD and GSH-Px, decreased TGF-ß1 and NO levels, downregulated iNOS and caspase-3 expression, upregulated ZO-1 expression, and maintained the integrity of the Sertoli cell junctions. Hence, L-Arg restored the normal testicular structure and function via its antioxidant, antiapoptotic, and antifibrotic effects.

Novel protective effect of diosmin against cisplatin-induced prostate and seminal vesicle damage: Role of oxidative stress and apoptosis.

Multiple organ toxicity has been associated with cisplatin (CIS) treatment, limiting its clinical use. The human prostate and seminal vesicles are accessory sex organs with androgen-dependent morphogenesis, growth, and secretion. The present study aimed to investigate, for the first time, the toxic effect of CIS on normal prostate and seminal vesicles in the presence and absence of diosmin (DS). The animals were randomized into 4 groups as follows: control (received vehicle), CIS group (7.5 mg/kg, i.p. on 5th and 12th day), DS group (100 mg/kg, p.o. for 15 days), and DS+CIS group. Histopathological and biochemical analyses were conducted to elucidate the goal of this study. CIS administration significantly induced prostate and seminal vesicle toxicity as evidenced by alteration of serum testosterone, LH, FSH, PSA, steroidogenic HSD17B6 as well as seminal analysis markers. Remarkably, marked histopathological changes in thin and ultrathin structures were observed. Besides, CIS significantly boosted oxidative stress as evidenced by the up-regulation of MDA and down-regulation of TAC. CIS significantly induced tissue apoptosis concomitant with suppression of cellular proliferation and stem cell expression as indicated by up-regulation of activated caspase-3 and Bax expression along with down-regulation of Bcl-2, Ki67, and CD44 expression. Interestingly, DS fixed all disturbances in the prostate and seminal vesicles induced by CIS. Together, CIS could cause prostate and seminal vesicle toxicity by affecting hormonal, steroidogenic, oxidative stress, apoptosis, and proliferation processes, and this effect was reversed by DS administration.

Efficacy of Levobupivacaine Versus Levobupivacaine Plus Dexmedetomidine Infiltration for Post-Tonsillectomy Analgesia: A Randomized Controlled Trial.

Background: The study evaluated the analgesic effects of levobupivacaine infiltration in the tonsil bed, and a combination of levobupivacaine and dexmedetomidine in patients undergoing tonsillectomy. Methods: Ninety children (ages 3 to 7 years) who were scheduled for a tonsillectomy were allocated randomly into two groups. (L Group): peritonsillar infiltration with 0.25% levobupivacaine (2 ml + 0.5 ml saline 0.9% per tonsil). (LD Group): levobupivacaine 0.25% (2 ml) plus dexmedetomidine 1 µg/kg diluted in 1 ml saline 0.9% (0.5 ml in each tonsil), and administered by peritonsillar infiltration (2.5 ml per tonsil) following intubation 3-5 minutes before operation. To avoid bias, infiltrate a total volume of 2.5 ml in each tonsil. The first analgesic request time was the primary outcome, with postoperative pain score, total analgesic consumption, total oral intake, sedation, and side effects as secondary outcomes. Results: The first rescue analgesia time in the LD group was longer (644.31 ± 112.89 min) than in the L group (551.51 ± 146.16 min, P-value <0.001). The number of patients who required >1 analgesic dose in the L group (n = 13) was higher than in the LD group (n = 5). The LD group consumes a lower total dose of IV paracetamol in the first 24 hours postoperatively (321.89 ± 93.25 mg) than the L group (394.89 ± 183.71 mg, P < 0.00-value < 0.050). On the first day postoperatively, patients in the LD group had a higher total oral intake (P < 0.001). Except for a slight increase in laryngospasm in the L group, there were no side effects. Conclusions: The Children's peritonsillar infiltration of levobupivacaine and dexmedetomidine improved postoperative pain after adenotonsillectomy. The topically applied levobupivacaine and dexmedetomidine were concomitant with no systemic effects, greater total oral intake on the first day postoperative, and higher family satisfaction.

COVID-19 associated mucormycosis in Assiut University Hospitals: a multidisciplinary dilemma.

Mucormycosis is a life-threatening opportunistic angioinvasive fungal infection. We aimed to describe the frequency, presentations, predictors, and in-hospital outcome of mucormycosis patients in the scope of CoronaVirusDisease-19 (COVID-19) during the third viral pandemic wave. This cross-sectional retrospective study included all patients who fulfilled the criteria of mucormycosis with concurrent confirmed covid19 infection admitted to Assuit University Hospital between March 2021 and July 2021. Overall, 433 patients with definite covid-19 infection, of which 33 (7.63%) participants were infected with mucormycosis. Mucormycosis was predominantly seen in males (21 vs. 12; p = 0.01). Diabetes mellitus (35% vs. 63.6%; p < 0.001), hypertension (2% vs.45.5%; p 0.04), and Smoking (26.5% vs. 54.5%; p < 0.001) were all significantly higher in mucormycosis patients. Inflammatory markers, especially E.S.R., were significantly higher in those with mucormycosis (p < 0.001). The dose of steroid intake was significantly higher among patients with mucormycosis (160 mg vs. 40 mg; p < 0.001). Except for only three patients alive by residual infection, 30 patients died. The majority (62%) of patients without mucormycosis were alive. Male sex; Steroid misuse; D.M.; Sustained inflammation; Severe infection were significant risk factors for mucormycosis by univariate analysis; however, D.M.; smoking and raised E.S.R. were predictors for attaining mucormycosis by multivariate analysis.

The protective effect of Lactobacillus acidophilus on experimental animals challenged with Trichinella spiralis; new insights on their feasibility as prophylaxis in Trichinella spiralis endemic area.

Trichinellosis is a common parasitic zoonosis. Complications of anthelmintic drugs combined with steroids raise the urge of alternative protective ways. The study aimed to investigate the protective effects of Lactobacillus acidophilus probiotic on both Trichinella spiralis adults and larvae in experimental animal models. Thirty-six male BALB/c mice were divided into 3 groups: negative control Group (G I); Group (G II) mice were inoculated orally by 500 Trichinella spiralis larvae; tested Group (G III) mice were prophylactic by an oral dose of Lactobacillus acidophilus in commercially available form for seven consecutive days, before infection. Mature worms and encysted larvae were counted on the 5th and 21st day post-infection (dpi), respectively. IL-1, IL-6, IL-10 and TNF-α concentrations were estimated at 5th and 21st dpi of all groups. Significant reductions in mean worms and larvae burden were detected by 62.1% and 73.5% in the prophylactic group compared to the non-prophylactic group. The cytokine profiles were revealed IL-1 and IL-6 up-regulation compared to IL-10 and TNF-α down-regulation in the tested group compared to other groups. Although Lactobacillus acidophilus failed to achieve complete eradication of Trichinella spiralis adults and larvae, it showed powerful effects in reducing parasites and cytokines burdens.

Interplay of Biochemical, Genetic, and Immunohistochemical Factors in the Etio-Pathogenesis of Gastric Ulcer in Rats: A Comparative Study of the Effect of Pomegranate Loaded Nanoparticles Versus Pomegranate Peel Extract.

BACKGROUND: Few data are available about the role of herbal extract loaded nanoparticles as an alternative safe medicine for the management of a gastric ulcer. AIM: This work is targeted at exploring the physiological effects of pomegranate loaded nanoparticles (PLN) against an indomethacin IND-induced gastric ulcer and comparing the results with traditional pomegranate peel extract (PPE). METHODS: Twenty-four rats were equally distributed into four groups: control, IND-treated, PLN-treated, and PPE-treated groups. Gross examination of gastric mucosa, and the calculation of ulcer and inhibition indices were done. Serum malondialdehyde (MDA), total antioxidant capacity (TAC), interleukin 2 (IL-2), IL-6, IL-10, gastric homogenate prostaglandin E2 (PGE2), and nitric oxide (NO) were estimated. Mucosal endothelial nitric oxide synthase (eNOS mRNA) expression was identified by qPCR. Histological and immuno-histochemical staining of Tumor necrosis factor-α (TNF-α) and eNOS of stomach mucosa were performed. RESULTS: In comparison with the control group, IND-treated rats showed visible multiple ulcers with ulcer index, serum MDA, IL-2 and IL-6 were elevated while IL-10, PGE2, NO, and eNOS mRNA expression were significantly reduced. Damaged surface epithelium with disrupted glandular architecture and heavy leucocyte infiltration of lamina propria was noticed. Immunohistochemical staining of stomach mucosa revealed marked increased TNF-α and reduced eNOS. Oral administration of PLN and PPE succeeded in improving the gross mucosal picture, and all biochemical, histological, and immunohistochemical alterations. CONCLUSION: Both PLN and PPE potently alleviated IND-induced gastric ulceration via increasing TAC, PGE2, NO, eNOS mRNA, and protein expression. However, the healing effect of PLN was obviously greater than PPE-treated rats.

Folic acid ameliorates neonatal isolation-induced autistic like behaviors in rats: epigenetic modifications of BDNF and GFAP promotors.

The current study investigated the role of epigenetic dysregulation of brain derived neurotrophic factor (BDNF) and glial fibrillary acidic protein (GFAP) genes and oxidative stress as possible mechanisms of autistic-like behaviors in neonatal isolation model in rats and the impact of folic acid administration on these parameters. Forty Wistar albino pups were used as follows: control, folic acid administered, isolated, and isolated folic acid treated groups. Isolated pups were separated from their mothers for 90 min daily from postnatal day (PND) 1 to 11. Pups (isolated or control) received either the vehicle or folic acid (4 mg/kg/day) orally from PND 1 to 29. Behavioral tests were done from PND 30 to 35. Oxidative stress markers and antioxidant defense in the frontal cortex homogenate were determined. DNA methylation of BDNF and GFAP genes was determined by qPCR. Histopathological examination was carried out. Neonatal isolation produced autistic-like behaviors that were associated with BDNF and GFAP hypomethylation, increased oxidative stress, increased inflammatory cell infiltration, and structural changes in the frontal cortex. Folic acid administration concurrently with isolation reduced neonatal isolation-induced autistic-like behaviors, decreased oxidative stress, regained BDNF and GFAP gene methylation, and ameliorated structural changes in the frontal cortices of isolated folic acid treated rats. Novelty: Neonatal isolation induces "autistic-like" behavior and these behaviors are reversed by folic acid supplementation. Neonatal isolation induces DNA hypomethylation of BDNF and GFAP, increased oxidative stress markers, and neuroinflammation. All of these changes were reversed by daily folic acid supplementation.

Glucagon-like peptide-1 analog improves neuronal and behavioral impairment and promotes neuroprotection in a rat model of aluminum-induced dementia.

BACKGROUND: Alzheimer's disease (AD) is a worldwide severe medical and social burden. Liraglutide (LIR) has neuroprotective effects in preclinical animal models. AIM: To explore the probable neuroprotective impact of Glucagon-like peptide-1 (GLP-1) on rats' behavior and to elucidate its underlying mechanisms. METHODS: A total of 24 male albino rats were assigned to control, LIR (300 µg/kg subcutaneously (s.c.)), AD only (100 mg/kg aluminum chloride (AlCl3 ) orally) and LIR + AD treated groups. Eight radial arm maze was performed. Serum blood glucose, proinflammatory cytokines, oxidative stress markers were measured and hippocampal tissue homogenate neurotransmitters were evaluated. Histopathological and immunofluorescent examinations were performed. RESULTS: LIR prevents the impairment of learning and improves both working memory and reference memory through significant reduction of serum tumor necrosis factor (TNF-α), interleukin 6 (IL-6) and interferon-γ (INF-γ) and malondialdehyde (MDA) and through the increase of superoxide dismutase (SOD), dopamine, adrenaline, and noradrenaline. LIR also improves hippocampal histological features of ALCL3 administrated rats and decreases the percentage of neuronal loss. CONCLUSION: LIR normalizes ALCL3 -induced dementia. It improves cognitive dysfunction and ameliorates cerebral damage.

The Role of Serum Procalcitonin Level as an Early Marker of Ascitic Fluid Infection in Post Hepatitic Cirrhotic Patients.

AIMS & BACKGROUND: The early diagnosis of spontaneous bacterial peritonitis (SBP) has been considered important in the overall patient's survival. Ascitic fluid culture examination performance, in the emergency setting, is time-consuming and not always available, so there is a need for easy to apply, rapid and reliable markers for diagnosis of patients with ascites. The present prospective study aimed to determine the early diagnostic value of serum procalcitonin (PCT) levels in decompensated cirrhotic patients (DCPs) with SBP. METHODS: 47 HCV cirrhotic patients with ascites were enrolled for this prospective study. The severity of cirrhosis was classified based on the Child-Pugh criteria. All patients were subjected to paracentesis and ascitic fluid (AF) culture. Serum PCT levels were measured using enzyme-linked fluorescence analysis (ELFA). RESULTS: The diagnostic value of serum PCT levels and WBC/PLT ratios for detecting infections were serum PCT levels (3.63 ± 3.47 ng/mL) in DCPs with infections which were significantly higher than in DCPs without infections (0.505 ± 0.230 ng/mL); p < 0.05. The cut-off value for serum PCT levels was 0.7 ng/mL for the diagnosis of infections in DCPs, for which the sensitivity and specificity were 93.1% and 73.2%, respectively. The AUC was 0.91 (95% CI: 0.83-0.99). CONCLUSION: Serum procalcitonin seems to provide satisfactory diagnostic biomarkers in SBP.

Neurobehavioral, testicular and erectile impairments of chronic ketamine administration: Pathogenesis and ameliorating effect of N-acetyl cysteine.

Ketamine, a dissociative anesthetic, recently has spread as a recreational drug. Its abuse lead to neurobehavioral disturbance in addition to toxic effects on other body organs. To evaluate the toxic effects of chronic administration of low ketamine doses on the memory, testicles, and erection, explore its pathophysiology through oxidative stress mechanism and examine the ameliorating effect of N-acetyl cysteine (NAC). A total of 40 male albino rats were assigned to control, vehicle, ketamine only I.P. (10 mg/kg), and ketamine (10 mg/kg) + NAC (150 mg/kg) groups. Assessment of memory affection and erectile function by Passive Avoidance, Novel Object Recognition, and copulatory tests were performed. Estimation of malondialdehyde (MDA), catalase (CAT), and total antioxidant capacity (TAC) in serum and prefrontal & hippocampal homogenate, and luteinizing hormone (LH), testosterone in serum were done. Prefrontal cortex, hippocampus, and testes were collected for histopathology. Chronic ketamine administration induced significant memory deficits (P < 0.05), reduced erectile function (P < 0.05), severe hypospermatogenesis, increased MDA, reduced CAT, TAC levels in serum, and tissue homogenate (P < 0.05) and reduction of LH, and testosterone (P < 0.05). Treatment with NAC resulted in significant improvement of memory function, improved erectile function, and decrease in oxidative injury in both serum and tissue homogenates. Testosterone and LH levels exhibited significant difference between treatment groups and controls (P < 0.05). NAC reduced the deleterious histopathological changes. These data suggest that long-term ketamine affects short and long memory, induces erectile and testicular dysfunction through oxidative stress. Co-administration with NAC ameliorates these toxic effects.

Aqueous garlic extract supresses experimental gentamicin induced renal pathophysiology mediated by oxidative stress, inflammation and Kim-1.

BACKGROUND: Gentamicin (Gent) has rapid & high bactericidal action in addition to its cheap price. Nevertheless, 30% of gentamicin-treated patients develop nephrotoxicity. OBJECTIVE: To explore the probable nephroprotective effects of the aqueous garlic extract (AGE) & to elucidate its underlying mechanisms via monitoring proinflammatory cytokines as tumer necrosis factor (TNF-α), interleukin 6 (IL-6) and interferon-γ (INF-γ), oxidative stess markers as malondialdehyde (MDA) & superoxide dismutase (SOD) & kidney injury molecule (Kim-1) as a promising early specific biomarker of renal dysfunction. METHODS: 32 adult male rats were divided into 4 equal groups treated for 21 days as: normal control group received normal saline orally, AGE-treated group received AGE at 250 mg/kg/day orally, Gent-treated group received Gent-sulphate intraperitoneal injection at 80 mg/kg /day, and AGE & Gent cotreated group received AGE and Gent concomitantly in the same previous doses. Serum urea, creatinine, glomerular filteration rate (GFR), systolic (SBP) and diastolic blood pressure (DBP), TNF-α, IL-6, INF-γ, MDA and SOD and Kim-1 mRNA expression were evaluated in kidney tissue homogenate. Renal cortex sections stained with Haematoxylin & eosin (H&E) were examined. RESULTS: AGE is nephroprotective through significantly reducing serum urea, creatinine, SBP and DBP, TNF-α, IL-6, INF-γ and MDA (the main product of lipid peroxidation), decreasing expression of Kim-1 mRNA in renal tissue and increasing level of GFR, the natural antioxidant SOD and improving renal histological features of Gent-treated rats. CONCLUSION: AGE normalizes Gent-induced renal dysfunction. Their co-administration is a plausible advice, although the therapeutic efficiency of Gent was not investigated.