The potential role of Tirzepatide as adjuvant therapy in countering colistin-induced nephro and neurotoxicity in rats via modulation of PI3K/p-Akt/GSK3-ß/NF-kB p65 hub, shielding against oxidative and endoplasmic reticulum stress, and activation of p-CREB/BDNF/TrkB cascade.

Although colistin has a crucial antibacterial activity in treating multidrug-resistant gram-negative bacteria strains; it exhibited renal and neuronal toxicities rendering its use a challenge. Previous studies investigated the incretin hormones either glucose-dependent insulinotropic polypeptide (GIP) or glucagonlike peptide-1 (GLP-1) for their neuroprotective and nephroprotective effectiveness. The present study focused on investigating Tirzepatide (Tirze), a dual GLP-1/GIP agonist, as an adjuvant therapy in the colistin treatment protocol for attenuating its renal and neuronal complications. Rats were divided into; The normal control group, the colistin-treated group received colistin (300,000 IU/kg/day for 7 days; i.p.). The Tirze-treated group received Tirze (1.35 mg/kg on the 1,4,7thdays; s.c.) and daily colistin. Tirze effectively enhanced histopathological alterations, renal function parameters, and locomotor activity in rats. Tirze mechanistically acted via modulating various signaling axes evolved under the insult of phosphatidylinositol 3-kinases (PI3K)/phosphorylated protein kinase-B (p-Akt)/ glycogen synthase kinase (GSK)3-ß hub causing mitigation of nuclear factor (NF)-κB (NF-κB) / tumor necrosis factor-α (TNF-α), increment of nuclear factor erythroid 2-related factor 2 (Nrf2)/ glutathione (GSH), downregulation of ER stress-related biomarkers (activation transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP)), antiapoptotic effects coupling with reduction of glial fibrillary acidic protein (GFAP) immunoreactivity and enhancement of phosphorylated c-AMP response element-binding (p-CREB) / brain-derived neurotrophic factor (BDNF)/tyrosine kinase B (TrkB) neuroprotective pathway. Briefly, Tirze exerts a promising role as adjuvant therapy in the colistin treatment protocol for protection against colistin's nephro- and neurotoxicity according to its anti-inflammatory, antioxidant, and antiapoptotic impacts besides its ability to suppress ER stress-related biomarkers.

Ocular findings in patients with cholestatic disorders of infancy: A single-centre experience.

BACKGROUND AND STUDY AIMS: Neonatal cholestasis can be associated with ocular findings that might aid in its diagnosis, e.g., Alagille syndrome (AGS) and Niemann Pick disease (NPD). We aimed to investigate the frequency of ocular manifestations in infants with cholestasis. PATIENTS AND METHODS: This cross-sectional study included cholestatic infants presenting to the Paediatric Hepatology Unit, Cairo University Paediatric Hospital, Cairo, Egypt. All infants underwent examination of lid, ocular motility, anterior and posterior segments and measurement of intraocular pressure, cycloplegic refraction, ocular ultrasonography and vision. RESULTS: The study included 112 infants with various cholestasis; 73 (65.2%) were males. The median age was 2months. Diagnosis was reached in 39 cases: 14 had AGS, 14 had biliary atresia (BA), 4 had NPD, 4 had post-haemolytic cholestasis, 2 had cytomegalovirus neonatal hepatitis, and one case had hepatorenal tyrosinaemia. Thirteen cases were probably having progressive familiar intrahepatic cholestasis (PFIC) type 1 or 2 considering their persistent cholestasis in the presence of normal gamma-glutamyl transpeptidase; 28 were left with a diagnosis of "idiopathic neonatal hepatitis" (INH), and 32 (28.6%) had no definite diagnosis. Ophthalmologic abnormalities were found in 39 cases (34.8%). The commonest finding was unilateral/bilateral optic nerve drusen in 12 (10.7%), followed by posterior embryotoxon in 11 (9.8%). Ocular findings were observed in 64.3% patients with AGS, 50% patients with NPD, 30.8% cases with suspected PFIC type 1or 2, 28.6% infants with INH, and 14.3% patients with BA. CONCLUSION: Ophthalmologic findings are not uncommon among cholestatic infants. Ophthalmologic examination should be routinely performed, including assessment of anterior segment, fundus examination, and ocular ultrasound.

Evaluation of some heavy metals residues in batteries and deep litter rearing systems in Japanese quail meat and offal in Egypt.

AIM: The main objectives of this study were for comparing the effect of batteries and deep litter rearing systems of domesticated Japanese quail, Coturnix coturnix japonica, on the concentration levels of cadmium, copper, lead, and zinc from the quail meat and offal in Ismailia, Egypt. MATERIALS AND METHODS: A total of 40 quail meat and their offal samples were randomly collected from two main quail rearing systems: Battery (Group I) and deep litter system (Group II) for determination of concentration levels of cadmium, copper, lead, and zinc. In addition, 80 water and feed samples were randomly collected from water and feeders of both systems in the Food Hygiene Laboratory, Faculty of Veterinary Medicine, Suez Canal University for heavy metals determination. RESULTS: The mean concentration levels of cadmium, copper, lead, and zinc in Group I were 0.010, 0.027, 1.137, and 0.516 ppm and for Group II were 0.093, 0.832, 0.601, and 1.651 ppm, respectively. The mean concentration levels of cadmium, copper, lead, and zinc in quail feed in Group I were 1.114, 1.606, 5.822, and 35.11 ppm and for Group II were 3.010, 2.576, 5.852, and 23.616 ppm, respectively. The mean concentration levels of cadmium, copper, lead, and zinc in quail meat for Group I were 0.058, 5.902, 10.244, and 290 ppm and for Group II were 0.086, 6.092, 0.136, and 1.280 ppm, respectively. The mean concentration levels of cadmium, copper, lead, and zinc for liver samples in Group I were 0.15, 8.32, 1.05, and 3.41 ppm and for Group II were 0.13, 8.88, 0.95, and 4.21 ppm, respectively. The mean concentration levels of cadmium, copper, lead, and zinc in kidney samples for the Group I were 0.24, 4.21, 1.96, and 4.03 ppm and for Group II were 0.20, 5.00, 1.56, and 3.78 ppm, respectively. Kidney had the highest concentration levels of heavy metals followed by liver then muscles. The highest concentration levels of copper were observed in liver samples. The order of the levels of these trace elements obtained from the four different quail organs is Ca > Pb > Zn > Cu. Lead and cadmium concentration levels in quail meat samples were exceeded the Egyptian standardization limits and suggesting a health threat from lead and cadmium to the quail consumers. CONCLUSION: Battery rearing system is more hygienic than deep litter system from the point of heavy metals pollution of water and feeds of quail. Feed samples from battery system had means concentration levels of lead not significantly higher (p>0.05) than those samples from deep litter system. Meanwhile, water samples from battery system had means concentration levels of cadmium, copper, and zinc significantly higher (p>0.05) than those samples from deep litter system. Quail may carry health risks to consumers.

Correlation of Serum CA-125 and Progesterone Levels with Ultrasound Markers in The Prediction of Pregnancy Outcome in Threatened Miscarriage.

BACKGROUND: The aim of this study was to evaluate the relationship between ultrasonographic findings and serum progesterone and cancer antigen-125 (CA-125) levels in threatened miscarriage and to predict pregnancy outcome. MATERIALS AND METHODS: In a prospective comparative case-control study, serum CA-125 and progesterone levels were measured for 100 pregnant women with threatened miscarriage who attended the outpatient clinic or the causality department of Obstetrics and Gynecology at Kasr El-Aini Hospital, Giza, Egypt, during the period from March 2013 to October 2013. Ultrasound was performed for fetal viability, crown-rump length (CRL), gestational sac diameter (GSD) and fetal heart rate (FHR). The patients were followed up and divided into two groups based on the outcome: 20 women who miscarried (group 1), and 80 women who continued pregnancy (group 2). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were tested for CA-125 and progesterone levels in prediction of the pregnancy outcome. Correlation of these chemical markers with the ultrasound markers was also examined. RESULTS: In the group that miscarried, CA-125 level was significantly higher (P<0.001) and serum progesterone level was significantly lower (P<0.001). For prediction of the outcome of pregnancy, the cut-off limit of 31.2 IU/ml for CA-125 level yielded sensitivity, specificity and an overall accuracy of 96.2, 100 and 99.4% respectively. The cut-off limit of 11.5 ng/ml for progesterone level yielded sensitivity, specificity and an overall accuracy of 97.5, 100 and 99.8% respectively. CA-125 level had a negative correlation with progesterone level and FHR levels (r=-0.716, P<0.001) and (r=-0.414, P<0.001) respectively. Serum progesterone level correlated with GSD (r=0.521, P<0.001) and with CRL (r=0.407, P<0.001) and FHR (r=0.363, P<0.001). CA-125 level was significantly higher in the group that showed hematoma as compared with the group without hematoma (P<0.001). Also, serum progesterone level was significantly lower in the group that showed hematoma as compared with the group without hematoma (P=0.017). CONCLUSION: Serum CA-125 and progesterone levels are valid early predictors of the outcome of pregnancy in women with threatened miscarriage. They are correlated with some ultrasonographic markers (GSD, CRL, and FHR).

A randomized controlled trial of clomifene citrate, metformin, and pioglitazone versus letrozole, metformin, and pioglitazone for clomifene-citrate-resistant polycystic ovary syndrome.

OBJECTIVE: To examine the efficacy of clomifene citrate, metformin, and pioglitazone versus letrozole, metformin, and pioglitazone among women with polycystic ovary syndrome (PCOS) resistant to clomifene citrate. METHODS: A prospective double-blind randomized controlled trial of women younger than 40 years who had primary/secondary infertility associated with PCOS and had not ovulated in response to clomifene citrate regimens previously was conducted at a center in Cairo, Egypt, between August 1, 2013, and December 31, 2014. Computer-generated random number tables and opaque envelopes were used to assign participants to group A or group B. Participants allocated to group A received 100mg clomifene citrate daily for 5 days from the third day of the menstrual cycle, whereas those in group B received 5mg letrozole daily in the same regimen. All patients received 850 mg metformin and 15 mg pioglitazone for 10 days from the first day of the menstrual cycle. The primary outcome was cumulative ovulation rate. Analyses were by intention to treat. RESULTS: Fifty women were assigned to each group. Ovulation occurred in 108 (92.3%) of 117 cycles in group A and 93 (86.9%) of 107 cycles in Group B (P=0.184). CONCLUSION: Combined treatment with letrozole, metformin, and pioglitazone was efficacious among women with PCOS resistant to clomifene citrate. ClinicalTrials.gov: NCT01909141.

Comparative study between different biomarkers for early prediction of gestational diabetes mellitus.

OBJECTIVE: To study various biomarkers in prediction of gestational diabetes mellitus (GDM). PATIENTS AND METHODS: Prospective observational study included 400 pregnant women. Maternal serum sex hormone binding globulin (SHBG), high-sensitive C-reactive protein (hs-CRP), uric acid, creatinine and albumin were measured before 15 weeks of gestation. Patients were followed-up for development of GDM. RESULTS: A total of 269 women were eligible for analysis. GDM complicated 27 (10.03%) of pregnancies. Hs-CRP levels were significantly higher and SHBG levels were significantly lower among women who subsequently developed GDM compared with normoglycemics. Uric acid, albumin and creatinine levels were not significantly different between both groups. For prediction of GDM, hs-CRP at a cutoff value of 2.55 mg/l showed a sensitivity and a specificity of 89% and 55%, respectively. SHBG at a cutoff value of 211.5 nmol/l showed a sensitivity and a specificity of 85% and 37%, respectively. Low SHBG with high hs-CRP predicted GDM with a sensitivity and specificity of 74.07% and 75.62%, respectively with an overall accuracy of 75.46%. CONCLUSION: Hs-CRP and SHBG are important early predictors of GDM. Adding SHBG to hs-CRP improves specificity and serves good overall accuracy. Uric acid, creatinine and albumin have no role in GDM prediction.

Vitamin D deficiency in Egyptian mothers and their neonates and possible related factors.

OBJECTIVE: To correlate vitamin D level in Egyptian mothers with that of their newborns, and examine risk factors related to maternal vitamin D deficiency. METHODS: A cross-sectional study was carried out at the university teaching hospital in Cairo, Egypt. Serum 25(OH) D levels were measured by enzyme-linked immunosorbent assay in 135 pregnant women at ≥37 weeks' gestation immediately before delivery and in cord blood of their newborns. RESULTS: The levels of serum 25(OH) D were 32.6 ± 21.4 ng/ml in mothers and 16.7 ± 10 ng/ml in their newborns. Maternal vitamin D level was strongly correlated with that of the newborns (r = 0.7, p < 0.0001). Maternal vitamin D deficiency/insufficiency and neonatal vitamin D deficiency/insufficiency were encountered in (40%, 28.9% and 60%, 32.6% respectively). Maternal vitamin D levels showed significant correlations with maternal body mass index (BMI; r = -0.201, p = 0.021), gestational age at delivery (r = 0.315, p ≤ 0.0001), fish consumption (r = 0.185, p = 0.032), educational level (r = 0.29, p = 0.001), and skin exposure (r = 0.247, p = 0.004). CONCLUSION: Maternal vitamin D levels strongly correlate with neonatal levels. Maternal vitamin D deficiency is a real problem in Egypt; this is generally related to high BMI, low fish consumption, low educational level, and limited skin exposure.