Early renal injury induced by caffeine consumption in obese, diabetic ZSF1 rats

Our previous studies indicate that prolonged caffeine consumption exacerbates renal failure in nephropathy associated with the metabolic syndrome. Reduced activity of the antioxidant defense system and beneficial effects of antioxidant therapy have been reported in diabetic rats and humans. The purpose of this study was to examine the early renal effects of caffeine consumption and the effects of concomitant antioxidant therapy in young obese, diabetic ZSF1 rats. Eleven-week-old male ZSF1 rats were randomized to drink tap water, caffeine (0.1%), tempol (1 mmol/L), or a solution containing caffeine and tempol for nine weeks. Caffeine significantly reduced body weight and glycosuria (weeks 2-9), improved glucose tolerance (week 9), had no effect on elevated plasma triglycerides, plasma cholesterol (week 9) and blood pressure (week 9), and significantly increased plasma cholesterol level (weeks 5 and 9). Yet, as early as after two weeks, caffeine greatly augmented proteinuria and increased renal vascular resistance (RVR) and heart rate (HR: week 9). Tempol had no effects on metabolic status and development of proteinuria, did not alter caffeine-induced metabolic changes and early proteinuria, and attenuated caffeine-induced increase in HR and RVR. Immunohistochemical analysis revealed significant glomerular and interstitial inflammation, proliferation, and fibrosis in control animals. Caffeine augmented the influx of glomerular and interstitial macrophages (ED1+ cells) influx, glomerular and tubular proliferative response, and glomerular collagen IV content. Tempol abolished the exacerbation of renal inflammation, proliferation, and fibrosis induced by caffeine. In conclusion, in nephropathy associated with the metabolic syndrome, caffeine--most likely through the interaction with adenosine receptors and interference with anti-inflammatory and/or glomerular hemodynamic effects of adenosine--augments proteinuria and stimulates some of the key proliferative mechanisms involved in glomerular remodeling and sclerosis. Tempol does not prevent early renal injury (i.e., proteinuria) induced by caffeine, yet abolishes late renal inflammatory, proliferative, and fibrotic change induced by chronic caffeine consumption in obese ZSF1 rats.     

Synthesis of pyrazolo[4',3':5,6]pyrano[2,3-d]pyrimidine derivatives for antiviral evaluation

6-Amino-3-methyl-4-(4-nitrophenyl)-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (1) was used as a precursor for preparation of some novel 3,7-dimethyl-4-(4-nitrophenyl)-2,4-dihydropyrazolo[4',3':5,6]pyrano[2,3-d]pyrimidine derivatives 3-6, and some of their corresponding N(2)- and C(5)-S-acyclic nucleosides 7 and 8. Furthermore, the preparation of 5-amino-1-[3,7-dimethyl-4-(4-nitrophenyl)-2,4-dihydropyrazolo[4',3':5,6]pyrano[2,3-d]pyrimidin-5-yl]-1H-pyrazole derivatives 10-16 were described. Some of the prepared products were selected and tested for antiviral activity against Herpes Simplex Virus type-1 (HSV-1).     

Melatonin and roentgen irradiation of the testis

Melatonin is a free-radical scavenger and antioxidant. Roentgen irradiation of testis (animal model formed of albino rats) was associated with destruction and depletion of the germinal epithelial cells. In roentgen-irradiated, melatonin-pretreated animals, these changes were markedly ameliorated. Thus administration of melatonin before irradiation can protect testis from some of the destructive effects of roentgen irradiation.     

Neurological complications of ankylosing spondylitis: neurophysiological assessment

Studies examined the neurological involvement of ankylosing spondylitis (AS) are limited. This study aimed to assess the frequency of myelopathy, radiculopathy and myopathy in AS correlating them to the clinical, radiological and laboratory parameters. Included were 24 patients with AS. Axial status was assessed using bath ankylosing spondylitis metrology index (BASMI). Patients underwent (a) standard cervical and lumbar spine and sacroiliac joint radiography, (b) somatosensory (SSEP) and magnetic motor (MEP) evoked potentials of upper and lower limbs, (c) electromyography (EMG) of trapezius and supraspinatus muscles. Patients’ mean age and duration of illness were 36 and 5.99 years. Bath ankylosing spondylitis metrology index mean score was 4.6. Twenty-five percent (n = 6) of patients had neurological manifestations, 8.3% of them had myelopathy and 16.7% had radiculopathy. Ossification of the posterior (OPLL) and anterior (OALL) longitudinal ligaments were found in 8.3% (n = 2) and 4.2% (n = 1). About 70.8% (n = 17) had ≥1 neurophysiological test abnormalities. Twelve patients (50%) had SSEP abnormalities, seven had prolonged central conduction time (CCT) of median and/or ulnar nerves suggesting cervical myelopathy. Six had delayed peripheral or root latencies at Erb’s or interpeak latency (Erb’s-C5) suggesting radiculopathy. Motor evoked potentials was abnormal in 54% (n = 13). Twelve (50%) and five (20.8%) patients had abnormal MEP of upper limbs and lower limbs, respectively. About 50% (n = 12) had myopathic features of trapezius and supraspinatus muscles. Only 8.3% (n = 2) had neuropathic features. We concluded that subclinical neurological complications are frequent in AS compared to clinically manifest complications. Somatosensory evoked potential and MEP are useful to identify AS patients prone to develop neurological complications.     

Circulating irisin and chemerin levels as predictors of seizure control in children with idiopathic epilepsy

Irisin and chemerin peptides expression are triggered by hypoxia and involved in activation of inflammatory cascades in various organs including the brain; however, their role in epilepsy is not fully illustrated. This study aims to explore the predictive role of irisin and chemerin for seizure control in children with idiopathic epilepsy. This cross-sectional comparative study included 50 children with idiopathic epilepsy; 25 of them had controlled seizures over the previous 6 months and 30 age- and sex-matched healthy children as controls. Epilepsy characteristics, seizure severity Chalfont score, and response to medications were assessed in relation to serum irisin and chemerin levels. In comparison to healthy controls, serum chemerin and irisin levels were significantly higher in children with idiopathic epilepsy especially those with uncontrolled seizures. Serum chemerin and irisin levels had significant positive correlation with seizure severity Chalfont score and the duration of epilepsy. Elevated Chalfont score (OR 3.19), serum chemerin (OR 2.01), and irisin (OR 2.03) are predictors of uncontrolled seizures. Circulating chemerin and irisin have 80% and 76% sensitivity and 88% and 92% specificity at cutoff point >?191.38 ng/ml and >?151.2 ng/ml respectively for prediction of uncontrolled seizures in children with idiopathic epilepsy. Elevated circulating level of irisin and chemerin may predict poor seizure control in children with idiopathic epilepsy suggesting the role of hypoxia-triggered neuroinflammation in the pathogenesis of childhood idiopathic epilepsy.     

Effect of maternal obesity on labor induction in postdate pregnancy

Objective

To test the hypothesis that there is a higher rate of unsuccessful induction of labor (IOL) in post-term obese pregnant women compared to non-obese ones.

Methods

In this prospective cohort study, 144 obese (BMI?>?30) and 144 non-obese (BMI?<?29.9) post-term (>?41 weeks) pregnant women were recruited. IOL was done by misoprostol or amniotomy and oxytocin infusion according to the Bishop score. Comparison of percentage of failed IOL in both groups (primary outcome) was performed by the Chi-test. Logistic regression and multivariable regression were performed to assess the odds ratio (OR) of cesarean section (CS) and coefficient of delay in labor till vaginal delivery (VD) in obese versus (vs) non-obese groups. Adjustment for gestational age, parity, Bishop Score, membrane rupture and amniotic fluid index was done in both regression analyses.

Results

CS rate was significantly higher in obese group [26.4 vs 15.9%; difference in proportion (95% CI) 0.1 (0.01, 0.19); P value 0.02]. 106 (73.6%) obese women and 121 (84.1%) non-obese women delivered vaginally. In addition, the duration till VD was significantly higher in obese group (22 vs 19 h, P value 0.01). After adjustment for possible confounding factors, the CS was still higher in the obese group in comparison to non-obese group (OR 2.02; 95% CI 1.1, 3.7; P value 0.02). This finding suggested that obesity was an independent factor for failure of IOL. In addition, after adjustment for these confounders, obesity had the risk of increasing labor duration by 2.3 h (95% CI 0.1, 4.5) in cases that ended in VD.

Conclusion

Based on our results, we conclude that there is a higher risk of CS in obese postdate pregnant women undergoing IOL in comparison to non-obese counterparts. Therefore, obstetricians should pay more attention to advising pregnant women about optimal weight gain during pregnancy and counseling about the chances of VD in cases of IOL.

ClincalTrial.gov ID

NCT02788305.

     

【In Press】 Long-term results of Ahmed glaucoma valve implantation in Egyptian population

AIM: To evaluate the long-term results and complications of Ahmed glaucoma valve (AGV) implantation in a cohort of Egyptian patients. METHODS: A retrospective study of 124 eyes of 99 patients with refractory glaucoma who underwent AGV implantation and had a minimum follow-up of 5y was performed. All patients underwent complete ophthalmic examination and intraocular pressure (IOP) measurement before surgery and at 1d, weekly for the 1, 3, 6mo, and 1y after surgery and yearly afterward for 5y. IOP was measured by Goldmann applanation tonometry and/or Tono-Pen. Complications and the number of anti-glaucoma medications needed were recorded. Success was defined as IOP less than 21 mm Hg with or without anti-glaucoma medication and without additional glaucoma surgery. RESULTS: Mean age was 23.1±19.9y. All eyes had at least one prior glaucoma surgery. IOP was reduced from a mean of 37.2±6.8 mm Hg to 19.2±5.2 mm Hg after 5y follow-up with a reduced number of medications from 2.64±0.59 to 1.81±0.4. Complete and qualified success rates were 31.5% and 46.0% respectively at the end of follow-up. The most common complications were encapsulated cyst formation in 51 eyes (41.1%), complicated cataract in 9 eyes (7.25%), recessed tube in 8 eyes (6.45%), tube exposure in 6 eyes (4.8%) and corneal touch in 6 eyes (4.8%). Other complications included extruded AGV, endophthalmitis and persistent hypotony. Each of them was recorded in only 2 eyes (1.6%). CONCLUSION: Although refractory glaucoma is a difficult problem to manage, AGV is effective and relatively safe procedure in treating refractory glaucoma in Egyptian patients with long-term follow-up. Encapsulated cyst formation was the most common complication, which limits successful IOP control after AGV implantation. However, effective complications management can improve the rate of success.     

Childhood glaucoma profile in Dakahelia, Egypt: a retrospective study

AIM: To analyze childhood glaucoma regarding its demographics, presentations, different causes and surgical modalities used among patients in Dakahelia and to apply the Childhood Glaucoma Research Network (CGRN) classification retrospectively to evaluate its convenience. METHODS: A retrospective study in which the medical files of all glaucoma patients <16 years old presented to Mansoura Ophthalmic Center, Mansoura University from 2014 to 2017, were retrieved and analyzed. Collected data included: age, gender, laterality, visual acuity (VA), refraction, intraocular pressure (IOP), corneal diameter, cup-disc ratio, types and number of surgeries and antiglaucomatous drugs (AGD) at the first and last visit. Prevalence of different subtypes was calculated and means of clinical features were compared. RESULTS: A total of 305 eyes of 207 patients were included classified into 6 groups: primary congenital glaucoma (PCG), juvenile open angle glaucoma (JOAG), glaucoma associated with systemic disease, glaucoma associated with ocular anomalies, acquired glaucoma and glaucoma following cataract surgery. PCG was the predominant type (55.1%) followed by acquired glaucoma (29.5%). Males represented 63.8% of the whole studied patients. Glaucoma associated with ocular anomaly group showed the youngest age at diagnosis (21.9±30.0mo). The shortest corneal diameter was recorded in post cataract group (10.4±0.5 mm). Highest cup-disc ratio was found in the PCG group (P<0.0005). Glaucoma associated with systemic disease presented with the highest baseline IOP (34.5±5.0 mm Hg). All the cases with PCG were treated surgically with 21.8% required more than one surgery. The majority of the patients (74.2%) in the acquired group were treated medically. Combined trabeculotomy-trabeculectomy was the most frequent operation done, accounting for 34.5% of all primary surgeries. Ahmed valve implantation comprised 87% of the secondary surgeries. Acquired glaucoma group had the highest percent of eyes with good final Snellen''s VA (69.4%), while glaucoma associated with ocular anomaly group had poorest final VA. CONCLUSION: PCG is the most prevalent type of childhood glaucoma, followed by acquired glaucoma especially traumatic hyphema. Combined trabeculotomy-trabeculectomy and Ahmed valve implantation are the most common surgical interventions. CGRN classification is found to provide a consensus skeleton and is recommended to be integrated in our routine ongoing clinical practice.