Carvacrol mitigates vancomycin-induced nephrotoxicity via regulation of IkBα/p38MAPK and Keap1/Nrf2 signaling pathways: an experimental study with in silico evidence.

OBJECTIVE: Despite its evident renal toxicity, vancomycin is considered an effective glycopeptide antibiotic against life-threatening positive bacterial contagions. The current study aimed to investigate the potential protective effects of carvacrol as well as its underlying mechanism against vancomycin-induced nephrotoxicity. MATERIALS AND METHODS: The animals were randomly classified into four groups (8 rats per group). Group I, which served as a control group, received only vehicles. Group II received a single i.p. injection of 50 mg/kg of carvacrol for seven days. Group III received vancomycin (200 mg/kg, i.p.) as a singular daily dose for seven days. Carvacrol was administered to Group IV seven days prior to the daily vancomycin dose. RESULTS: The results revealed that carvacrol minimized vancomycin-induced renal injury as evidenced by lower serum cystatin C levels and kidney injury molecule-1 (KIM-1), in addition to a decline in renal damage caused by vancomycin as indicated in histopathological assessment. Furthermore, carvacrol significantly attenuated oxidative stress parameters and inflammatory mediators. Moreover, it downregulated Keap1, mitogen-activated protein kinase (p38MAPK), and nuclear factor kappa B (NF-κB) genes and proteins, along with controlling the NF-κB inhibitory protein (IkBα) and nuclear factor erythroid 2-related factor 2 (Nrf2) genes and proteins observed through streaming its genes. A molecular docking technique was also used to investigate the potential interactivity between carvacrol and proteins involved in regulating oxidative injury and inflammatory responses. CONCLUSIONS: The current study findings revealed that carvacrol administration before vancomycin could be a promising therapeutic approach for maceration of renal damage stimulated by vancomycin via controlling IkBα/MAPK and Keap1/Nrf2 signaling molecules.https://www.europeanreview.org/wp/wp-content/uploads/graphical-abstract-1.jpg.

Multiple targets of Nrf 2 inhibitor; trigonelline in combating urethane-induced lung cancer by caspase-executioner apoptosis, cGMP and limitation of cyclin D1 and Bcl2.

OBJECTIVE: Among other types of cancerous lesions, lung cancer is one of the prevalent causes of death. Trigonelline is a plant alkaloid, a significant constituent in coffee, and has shown health benefits in several disorders. The present study aims to investigate the potential therapeutic role of trigonelline in lung cancer. MATERIALS AND METHODS: Seventy-five BALB/C mice were assigned to five groups and treated for 150 days as follows (1): normal control group; (2) trigonelline only (50 mg/kg/ P.O) daily for the last thirty days; (3) urethane (1.5 g/kg B.w/i.p) at day one and sixty; (4) urethane and carboplatin (15 mg/kg i.p) for the last thirty days; and (5) urethane and trigonelline for the last thirty days. Tumor size was measured while blood and lung were collected for biochemical, western blotting analysis, and histological examinations. RESULTS: Urethane demonstrated significant changes in all biochemical and molecular parameters and histological examinations. In animals pretreated with urethane, trigonelline significantly reduced tumor size and restored Nrf2, NF-кB p65, Bcl-2, Cyclin D1, ICAM-1, and MMP-2, along with improving cGMP and active caspase three and refining histological architectures. CONCLUSIONS: Nrf2 signaling may be a promising therapeutic target for adenocarcinoma protection or management. Due to its multiple therapeutic effects on Nrf2, cyclin D1, NF-кB pathways, and the BAX/Bcl2 axis, trigonelline significantly induced cell cycle arrest and apoptosis.https://www.europeanreview.org/wp/wp-content/uploads/Graphical_Abstract-1.jpg.

Efficacy and tolerability of combination cisplatin and ifosfamide chemotherapy with vaginal cuff brachytherapy in the first line treatment of uterine carcinosarcoma.

PURPOSE OF INVESTIGATION: A retrospective study to evaluate six cycles of cisplatin 40 mg/m2 on day 1 and ifosfamide 1,200 mg/m2 daily on days 1 to 4 with Mesna every four weeks as first line treatment for 29 patients with a diagnosis of uterine carcinosarcoma. MATERIALS AND METHODS: A total of 23 of 29 patients received high dose rate intracavitary vaginal cuff brachytherapy (VCBT) with two fractions of seven Gy each. Median age was 65 years (range 40-82); 13 (44.8%) had Stage I disease, three (10.3%) had Stage II, eight (27.6%) had Stage III, and five (17.2%) patients had Stage IV disease. RESULTS: Most common toxicities were anemia grade 1 (35%)/grade 2 (45%), and neutropenia grade 3 (17%)/grade 4 (6.9%). Eleven dose modifications, four treatment discontinuations, and one patient withdrawal occurred. At a median follow up of 45 months (range 9 to 144), Progression free survival (PFS) was 20% and overall survival (OS) was 40% for Stage IV, PFS 75% and OS 62.5% for Stage III, compared to a PFS 75% and OS 72.2% for Stages I-II. Median OS for the entire group was 12.43 years (95% CI 3.69 to inf); for Stage I-III 12.4 years (6.1 to inf), and for Stage IV 15.6 months (95% CI 9.4 to inf). CONCLUSIONS: Cisplatin and ifosfamide chemotherapy with VCBT was well tolerated and has promising activity in uterine carcinosarcoma.

Screening for diabetes in Kuwait and evaluation of risk scores.

This study aimed to develop a simple risk score to identify individuals at high risk for undiagnosed diabetes in the Kuwaiti adult population and to assess the performance of previously published diabetes risk scores. A cross-sectional survey with a sample of 562 Kuwaiti public sector employees was carried out in 2007. Data were collected through a self-administered questionnaire and a blood glucose test. The overall prevalence of diabetes using American Diabetes Association 2003 criteria was 21.4% (4.1% newly detected). The proposed score had 87% sensitivity and 64% specificity in predicting undetected diabetes using only 4 questions (age, waist circumference, use of blood pressure medication and diabetes in a sibling). Most previously published risk scores were not applicable to this population.

Screening for diabetes in Kuwait and evaluation of risk scores

This study aimed to develop a simple risk score to identify individuals at high risk for undiagnosed diabetes in the Kuwaiti adult population and to assess the performance of previously published diabetes risk scores. A cross-sectional survey with a sample of 562 Kuwaiti public sector employees was carried out in 2007. Data were collected through a self-administered questionnaire and a blood glucose test. The overall prevalence of diabetes using American Diabetes Association 2003 criteria was 21.4% [4.1% newly detected]. The proposed score had 87% sensitivity and 64% specificity in predicting undetected diabetes using only 4 questions [age, waist circumference, use of blood pressure medication and diabetes in a sibling]. Most previously published risk scores were not applicable to this population

Loss of vision: a manifestation of TURP syndrome. A case report.

We report a case of transient blindness, part of a TURP syndrome, in a 65 year old man undergoing TUR of the prostate under centro-neuron block. Irrigating fluid consisted of 1.5% glycine. As a result, serum levels of glycine increased to 12,470 mols.l-1 (N176-332 mumols.l-1). We attribute this loss of vision to glycine toxicity.

An investigation on the shear bond strength of one dentin adhesive at two different dentin depths.

The aim of this investigation was to study the effect of dentin depth and patient's age on the shear bond strength of one dentin adhesive (ART Bond), using an Instron Universal testing machine at a cross-head speed of 0.5 mm/min. Forty human molar teeth were used and were divided into two main groups, twenty each representing two age groups of patients, i.e., between 20 to 30 years and between 30-40 years of age. Every group was further subdivided into two subgroups of different dentin depths, i.e., superficial and deep. Results were recorded in Kg/Cm2 and converted into MPa units, then tabulated and statistically analyzed. A Duncan's range statistic test at P < or = 0.05 showed statistically significant differences between the bond strength values for both age groups at different dentin depths, with the superficial dentin showing higher bond values, and there were also statistically significant differences between the bond strength values of the two age groups at the same dentin depth, with the older age group showing higher bond values.

Volvulus of the sigmoid colon in Jordan.

This report discusses 27 patients with sigmoid volvulus treated at Jordan University Hospital (JUH) during a 15-year period. These patients represented 4.7 percent of adult patients treated for intestinal obstruction in the same period. The average age was 54.5 years, and none of the patients was institutionalized. Twenty-five patients presented with acute symptoms, and two had chronic symptoms. Sigmoidoscopic detorsion was achieved in 15 patients. Emergency resection was required in two of these patients: for the development of gangrene a few hours after detorsion in one patient and for recurrence within 24 hours in the other despite the presence of a rectal tube. Early recurrence occurred in two other patients and was managed endoscopically. Emergency surgery was performed in 10 other patients: for a failed endoscopic detorsion in three patients, for ulcerated and bleeding mucosa forecasting gangrene in another, and as a primary treatment in six patients who were either misdiagnosed or suspected to have gangrenous bowel. Elective resection was performed in 13 patients. The mortality rate was 15 percent (4/27) for the whole series and 33.3 percent (1/3) for those with gangrenous bowel.

Adrenal cysts: diagnosis and management.

We present 7 patients (5 adult females and 2 neonate males) with adrenal cysts. The cysts included 1 hydatid, 1 lymphatic and 5 pseudocysts. Three cysts were diagnosed preoperatively and all were resected surgically. The existence of true epithelial cysts of the adrenal gland is doubted by many authors; the present series includes most types of adrenal cyst.

Increased transfer of iron to the fetus after total dose infusion of iron dextran during pregnancy.

After total dose infusion of iron dextran to 14 pregnant women the saturation of transferrin and the concentration of ferritin were increased in the cord blood at birth, compared with untreated cases. These changes suggest that the fetal iron stores may be increased by such treatment.

Diverticular disease of the colon in Jordan.

In a case review over a nine-year period, 35 patients were referred to the University Hospital with a variety of abdominal symptoms related to the gastrointestinal tract, were found to have diverticular disease of the colon. In a retrospective evaluation of 274 consecutive barium enemas performed at the same institute in patients aged 20 to 85 years, in a three-year period (1979 to 1981), colonic diverticula were found in 11 patients, giving incidence of 4 per cent; all positive enemas for diverticulosis in this group occurred in patients over the age of 40 years.