Biochemical changes in the fallopian tube and uterus of the rhesus monkey (Macaca mulatta) under the influence of progestational contraceptive steroids.

The effect of oral administration of progestational contraceptive steroids such as megestrol acetate (MGA), norethynodrel (NE) and ethynodiol dliacetate (EDA), on the reproductive organs of rhesus monkeys has been studied. The ovarian weight was raduced by MGA whereas, NE enhanced the weight of the Fallopian tube, uterus, ovary, adrenal and pituitary and EDA that of the Fallopian tube only.Treatment with MGA caused a rise in the levels of lactic acid and non-protein nitrogen (NPN), fall in the levels of glycogen and no alteration of the protein concentration of the Fallopian tube and uterus. Further, a marked Inhibition of the activities of β -glucuronidase, adenosine triphosphatase (ATPase), alkaline phosphatase, malic dehydrogenase (MDH) and enhancement of those of acid phosphatase, lactic dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (G-6-PD) were observed in both tissues.As a result of the treatment with NE, the Fallopian tube and uterus recorded a significant increase in the concentrations of protein and glycogen; however, the NPN level of the tube was diminished and that of the uterus was enhanced. On the other hand, depression of the activities of β -glucuronidase and LDH and stimulation of those of ATPase, MDH and alkaline phosphatase were observed in both tissues. However, acid phosphatase activity of the uterus and G-6-PD activity of the tube were reduced markedly.     

Calciphylaxis in pediatric end-stage renal disease

Calciphylaxis is a rare, but life-threatening complication of end-stage renal disease (ESRD) that has been reported mostly in adult patients. The exact etiology is unknown, but the disease is commonly associated with a high calcium-phosphorus product and elevated levels of parathyroid hormone (PTH). We herein review the published reports on calciphylaxis in ESRD patients less than 18 years old and report the case of a patient with severe calciphylaxis who presented with lower extremity pain, muscle tenderness and difficulty in walking. The serum PTH was low, and the calcium-phosphorus product was normal. The diagnosis of calciphylaxis was confirmed by a muscle biopsy. Treatment with low calcium peritoneal dialysate and substitution of calcium-based phosphorus binders with sevelamer (Renagel) was unsuccessful. The patients clinical condition progressed to extensive soft tissue calcification and ulcerating skin lesions. Nine months after the onset of symptoms, the patient died of cardiopulmonary arrest.     

Matrix metalloproteinase-2, squamous cell carcinoma antigen, and tissue polypeptide-specific antigen expression in Egyptian patients with cervical carcinoma: Relationship with prognosis

Matrix metalloproteinases (MMPs), a family of proteolytic enzymes produced by both stromal and tumor cells, appear to have a key role in the events leading to local invasion and metastasis by malignant neoplasms. In the present study, we evaluated the role of MMP-2, squamous cell carcinoma antigen (SCCA), and tissue polypeptide - specific antigen (TPS) in cervical neoplasia. Using Western blotting and enzyme immunoassay (EIA), we analyzed 50 patients with cervical carcinoma (CC) and 25 normal controls for expression of MMP-2 in tissue cell lysates. We also quantified SCCA and TPS with microparticle immunoassay and EIA, respectively. The results were correlated with human papilloma virus (HPV) infection, clinicopathological findings, and disease outcome. The cutoff point for each marker was estimated from receiver operating characteristic curves. Logistic regression analysis was performed to estimate the odds ratio (OR) and 95% confidence interval (CI) for each marker. MMP-2, SCCA, and TPS protein expression were significantly higher in patients with CC than in normal controls. While TPS was the best marker for discriminating between patients and controls, MMP-2 was associated with an advanced tumor stage (OR, 13.9 [95% CI, 1.4-133.9]) and poor histological grade (OR, 10.2 [95% CI, 1.7-60.5]). Moreover, independent of the effect of an advanced CC stage and grade, the patients' age, and the presence of HPV infection, MMP-2 was considered a strong predictor for CC recurrence (OR, 8.1 [95% CI, 1.3- 49.1]). Tissue markers may be used to select high-risk patients for early detection of and adjuvant therapy for recurrence. Our MMP-2 findings are particularly relevant to the development of protease inhibitors as a new cancer therapy approach.     

Immunofluorescent labeling of increased calpain expression and neuronal death in the spinal cord of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice

Parkinson's disease (PD) is a movement disorder characterized by rigidity, tremor, and bradykinesia, originating from degeneration of dopaminergic neurons in the substantia nigra (SN), retrorubral area, and locus ceoruleus (LC). Calpain has been implicated in the pathophysiology of neurodegenerative diseases. Since the spinal cord (SC) and brain are integrally connected and calpain is involved in cell death and mitochondrial dysfunction, we hypothesized that SC neurons are also affected in PD. In order to examine this hypothesis, we examined both brain and SC from mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). To identify cells expressing calpain, double immunofluorescent labeling was performed with antibodies specific for calpain and a cell type (OX-42, GFAP, or NeuN). Combined terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and double immunofluorescent labeling were used to identify death of specific cells in the central nervous system (CNS). There was an increase in calpain expression in microglia, astrocytes, and neurons in the SC of MPTP-treated mice at 1 and 7 days, as compared to controls. TUNEL-positive neurons in the SC and SN showed apoptotic characteristics. These results demonstrated that neuronal death occurred not only in SN but also in the SC of MPTP-treated mice and has provided evidence for a possible calpain-mediated SC neuronal death in MPTP-induced parkinsonism in mice.     

Renal papillary necrosis induced by naproxen

A 17-year-old healthy girl was admitted to our hospital with diffuse abdominal pain and decreased oral intake of about 11 days duration. About a week prior to admission, she had taken naproxen, 250 mg four times a day for 4 days. Physical examination was normal except for diffuse abdominal tenderness on deep palpation. Investigations revealed high serum BUN (42 mg/dl) and creatinine (4.0 mg/dl). Serum electrolytes and complement (C3, C4) levels and urinalysis were normal. Antinuclear-antibody and anti-dsDNA were negative. Kidney biopsy revealed renal papillary necrosis, acute tubular necrosis, and focal interstitial nephritis. A diagnosis of nonoliguric acute renal failure due to naproxen nephrotoxicity was made. She received intravenous hydration, and oral steroids, which was gradually discontinued in 3 months. A follow-up at 4 months revealed normal renal function with a serum creatinine of 1.1 mg/dl, BUN 7 mg/dl, and normal urinalysis. The report highlights a need for caution while using naproxen or any other nonsteroidal anti-inflammatory drugs, even for a short duration.     

Effect of highly purified urinary follicle-stimulating hormone on oocyte and embryo quality

OBJECTIVE: To determine the effects of ovarian stimulation with highly purified urofollitropin on oocyte and embryo quality. DESIGN: Parallel randomized open-label clinical study. SETTING: Assisted reproduction centers. PATIENT(S): Two hundred sixty-seven infertile couples undergoing IVF/ICSI. INTERVENTION(S): All participants underwent standard down-regulation with GnRH analogue. One hundred thirty-three participants received highly purified urinary FSH and 134 controls received recombinant FSH. MAIN OUTCOME MEASURE(S): Primary end points were number of morphologically mature oocytes retrieved, embryo quality, and pregnancy and implantation rates. Secondary end points were: total number of days of FSH stimulation, total dose of gonadotropin administered, fertilization rate per number of retrieved oocytes, embryo cleavage rate, live birth and miscarriage rates, endometrial thickness and estradiol level on the day of hCG administration, cancellation rate, and incidence of moderate or severe ovarian hyperstimulation syndrome. RESULT(S): Pregnancy and implantation rates were nonsignificantly higher in the urinary FSH group than the recombinant FSH group (46.5% vs. 36.8% and 22.1% vs. 15.8%, respectively). The grade 1 embryo score was significantly higher in the urinary FSH group than the recombinant FSH (42.1% vs. 33.5%), and the live birth rate was nonsignificantly higher in the former group. CONCLUSION(S): Highly purified urinary FSH is as effective, efficient, and safe for clinical use as recombinant FSH.     

Influence of the use of phosphate binders on serum levels of calcium phosphate in patients with chronic kidney disease undergoing hemodialysis: A retrospective and prospective study

Hypercalcemia–hyperphosphatemia is an unavoidable consequence of end-stage chronic kidney disease and common in hemodialytic patients. Calcium carbonate (CaCO₃) is one type of phosphate binder used widely and prescribed in patients undergoing hemodialysis, aiming to control the levels of calcium and phosphate. These drugs are most effective if taken with meals. This study aimed to evaluate the use of phosphate binders in hemodialysis patients and the factors that influence the success of phosphate binder therapy by experimental studies with retrospective data collection through the medical records and prospectively through the questionnaire and interviews with patients. The research was conducted in the Unit Hemodialysis building floor 8 of Cipto Mangunkusumo Hospital, Jakarta. The data were collected in a retrospective way for two months (January–February 2013) and a prospective study in March–April 2013. Patients included were stage 5 chronic kidney disease patients who underwent hemodialysis in hemodialysis ward of Cipto Mangunkusumo Hospital. Patients who had data of serum levels at the beginning of the use of calcium phosphate and the final data in 2013 got the phosphate binder therapy.

Results

Ninety six patients with stage 5 chronic kidney disease who underwent hemodialysis had been using phosphate binder for 3 years in average. Patient evaluation showed that hypocalcemia was obtained in 23%; normokalemia in 42.7% and hypercalcemia in 34.3%. While the percentage of patients with hipofosfatemia14, 6%, normofosfatemia 32.3% and 53.1% hyperphosphatemia. Results obtained by the prospective analysis of factors that affect the success of the use of phosphate binder therapy are related to how the routine use of phosphate binders is made by the patient. Chi square test showed a significance of 0.000 (p < 0.05), the effect of 54%.

Conclusion

We can conclude there are many events happening such as hyperphosphatemia in hemodialysis patients that use phosphate binders. Monitoring of serum levels of calcium phosphate in patients with chronic kidney disease undergoing hemodialysis should be performed every month. Education and the role of clinical staff required to assist compliance and therapeutic efficacy of phosphate binder are necessary.