Cardamonin exerts a protective effect against autophagy and apoptosis in the testicles of diabetic male rats through the expression of Nrf2 via p62-mediated Keap-1 degradation

Cardamonin (CARD) is a chalconoid with anti-inflammatory and antioxidant properties, and it is present in several plants. We sought to explore whether CARD exerts any positive effects against hyperglycemia-induced testicular dysfunction caused by type 2 diabetes and aimed to identify its possible intracellular pathways. Adult male rats were subdivided into six groups: control, CARD, diabetic (DM), DM + glibenclamide (GLIB), DM + CARD and DM + GLIB + CARD. Type 2 DM induced a significant increase in blood glucose and insulin resistance, along with diminished serum insulin, testosterone and gonadotropins levels, which were associated with the impairment of key testicular androgenic enzymes and cellular redox balance. Administration of CARD at a dose of 80 mg/kg for 4 weeks effectively normalized all of these alterations, and the improvement was confirmed by epididymal sperm analysis. After treatment with CARD, the pathological changes in spermatogenic tubules were markedly improved. Significantly, CARD upregulated testicular glucose transporter-8 (GLUT-8) expression and had inhibitory effects on elevated autophagy markers and caspase-3 immunoreactive cells. Furthermore, our results revealed that CARD was able to attenuate damage via activation of Nrf2 through the p62-dependent degradation of testicular anti-Kelch-like ECH-associated protein-1 (Keap-1). In conclusion, this study suggests that CARD provides protection against diabetic stress-mediated testicular damage. The use of CARD with conventional anti-diabetic therapy was associated with improved efficacy compared with conventional therapy alone.

Cardamonin exerts a protective effect against autophagy and apoptosis in the testicles of diabetic male rats through the expression of Nrf2 via p62-mediated Keap-1 degradation

Cardamonin (CARD) is a chalconoid with anti-inflammatory and antioxidant properties, and it is present in several plants. We sought to explore whether CARD exerts any positive effects against hyperglycemia-induced testicular dysfunction caused by type 2 diabetes and aimed to identify its possible intracellular pathways. Adult male rats were subdivided into six groups: control, CARD, diabetic (DM), DM + glibenclamide (GLIB), DM + CARD and DM + GLIB + CARD. Type 2 DM induced a significant increase in blood glucose and insulin resistance, along with diminished serum insulin, testosterone and gonadotropins levels, which were associated with the impairment of key testicular androgenic enzymes and cellular redox balance. Administration of CARD at a dose of 80 mg/kg for 4 weeks effectively normalized all of these alterations, and the improvement was confirmed by epididymal sperm analysis. After treatment with CARD, the pathological changes in spermatogenic tubules were markedly improved. Significantly, CARD upregulated testicular glucose transporter-8 (GLUT-8) expression and had inhibitory effects on elevated autophagy markers and caspase-3 immunoreactive cells. Furthermore, our results revealed that CARD was able to attenuate damage via activation of Nrf2 through the p62-dependent degradation of testicular anti-Kelch-like ECH-associated protein-1 (Keap-1). In conclusion, this study suggests that CARD provides protection against diabetic stress-mediated testicular damage. The use of CARD with conventional anti-diabetic therapy was associated with improved efficacy compared with conventional therapy alone.

accuracy of PET-CT scan in detecting axillary lymph node metastasis in breast cancer

Objective: To evaluate the accuracy of positron emission tomography CT scan in detecting axillary lymph node metastases compared to the pathology results in patients with primary breast cancer

Setting: Breast Surgery Unit, King Hamad University Hospital, Bahrain

Design: A Retrospective Comparative Study

Method: Twenty-one newly diagnosed females with invasive breast cancer and staged using FDGPET-CT scan. Images were evaluated by two experienced radiologists for any abnormal increase in axillary FDG uptake. Imaging results were compared to axillary lymph node pathology, such as sentinel lymph node biopsy, FNA cytology from axilla or axillary clearance

Result: All patients had histopathology results that matched the PET-CT finding except 2 [10%] patients who matched the CT scan alone but not the PET scan. The sensitivity of the PET-CT for detection of axillary lymph node metastasis in this series was 80% and the specificity was 100%. Both sensitivity and specificity were noted to be high compared to other published data

Conclusion: PET-CT scan is highly sensitive and specific in detecting axillary lymph nodes metastases in breast cancer. The sensitivity reached 80% and the specificity was 100% in our study; this could be attributed to the small number of patients and the improvement in the new generation of the PET-CT scanners with high resolution, which led to further increase in the diagnostic value. Therefore, recent evidence does not support the use of PET-CT scan to replace clinically negative axillary lymph nodes as initial assessment

Effectiveness of intensive insulin therapy in the management of acute necrotizing pancreatitis induced by very severe hypertriglyceridemia

Hypertriglyceridemia may be responsible for up to 4% of acute pancreatitis. Complicated pancreatitis is a serious medical condition and might be fatal. Therefore, treating the underlying cause along with supportive measures is crucial to prevent further deterioration and possible death. There have been reports where Insulin has been the mainstay of treatment for reducing triglyceride levels in patients with pancreatitis, however, there are no well-established guidelines. We present a forty-year-old female patient diagnosed with acute necrotizing pancreatitis. CT abdomen revealed acute necrotic pancreatitis [Balthazar E] with extensive peri-pancreatic and peritoneal fluid collections. The patient was managed in the ICU for 28 days. She continued to receive gemfibrozil and insulin infusion, initiated according to the ICU's Protocol - Algorithm 1 targeting glucose values of 4.4 mmol/L to 10 mmol/L along with heparin infusion. She was successfully treated and recovered. She was discharged on antidiabetic and lipid lowering medications

Surgical management of Necrotizing Enterocolitis following Congenital Diaphragmatic Hernia Repair

Necrotizing Enterocolitis [NEC] is a significant cause of in-hospital mortality. The pathogenesis remains unclear, but may be associated with Staphylococcus epidermidis related sepsis, hypertonic feeds or other stress. It is also associated with Abdominal Compartment Syndrome [ACS] as documented after complete closure of gastroschisis. While the incidence of NEC is rare, the associated mortality is significant. We report a case of NEC following the repair of a congenital diaphragmatic hernia [CDH]; an unusual yet serious complication. A literature search revealed only one similar case which resulted in mortality. The possibility of serious postoperative complications following the repair of CDH must be considered in any neonate who exhibits deterioration in their general condition

Thymus and activation-regulated chemokine in children with systemic lupus erythematosus

Systemic Lupus Erythematosus [SLE] is an autoimmune rheumatic disease and glomerulonephritis is a challenging complication of SLE which is more frequent in children. Thymus and activation - regulated chemokine [TARC] is a hemostatic chemokine and TARC production is induced rapidly thus providing an important link between early innate immune responses and adaptive immunity. The aim of the present work was to measure serum TARC in SLE patients and correlate it with disease activity in patients with clinically evident lupus nephritis versus patients without lupus nephritis. This study was conducted on thirty patients [26 females and 4 males] with SLE, regularly attending the Pediatric Allergy and lmmunology Clinic Children's Hospital, Ain Shams University. Their ages ranged between 9-16 years [mean +/- SD = 13.6 +/- 2.68 years]. Lupus patients were categorized into two groups according to lupus nephritis [LN]: Group I a [with LN] and Group I b [without LN]. Results of the previous two groups were compared to a control group comprised of 40 [27 females and 13 males] age and sex matched apparently healthy subjects whose ages ranged between 10 and 16 years [mean + SD= 12.95 +/- 2.68 years]. All participants were subjected to full history taking, thorough clinical examination, urine analysis, assessment of ESR, creatinine, C3, ANA Abs, anti-dsDNA Abs and serum TARC. All SLE patients were seropositive for ANA. Serum TARC levels were statistically highly significantly [p=<0.001] elevated in all lupus patients, in Group Ia, in Group lb all respectively compared to controls and also in Group Ia versus Group lb. As regards indicators of LN, serum TARC showed statistically highly significant [p<0.001] elevated levels in patients with hematuria, edema, hypertension and anti-dsDNA positivity than in those with negative indicators of LN. Serum TARC showed statistically significant [p<0.05] positive correlation with ESR and SLEDAT score in all lupus patients, statistically highly significant [p=<0.001] positive correlation with ESR [in group I a], 24 hrs urinary proteins [in all lupus patients and group I b] and serum creatinine [in all lupus patients, group I a and group I b]. In conclusion, serum TARC levels were statistically significantly higher in all lupus patients versus healthy controls being statistically significantly higher in LN patients with versus lupus patients without nephritis. Also, serum TARC had significant positive correlation to SLEDAI score and ESR indicating its correlation with disease activity