Spinal cord injury induced arrest in estrous cycle of rats is ameliorated by S-nitrosoglutathione: novel therapeutic agent to treat amenorrhea

IntroductionAmenorrhea following spinal cord injury (SCI) has been well documented. There has been little research on the underlying molecular mechanisms and therapeutics.AimThe purpose of the present study was to investigate the effect of GSNO in ameliorating SCI‐induced amenorrhea through affecting the expression of CX43, NFkB, and ERβ protein.MethodsSCI was induced in female SD rats at the T9‐T10 level. Estrous stage was determined by vaginal smear. GSNO (50 µg/kg body weight) was gavage fed daily. Animals were sacrificed on day 7 and 14 post SCI. Ovaries were fixed for histological and biochemical studies. Expression levels of ERβ, CX‐43, and NFkB were analyzed by Western blot and immunofluorescence.Main Outcome MeasuresGSNO hastens resumption of the estrous cycle following SCI‐induced transient arrest.ResultsResumption of estrous cycle was hastened by GSNO. Atretic and degenerating follicles seen in the ovary of SCI rats on day 14 post‐SCI were decreased in GSNO treated animals. The increased CX43 expression observed with SCI ovary was decreased by GSNO. ERβ expression decreased significantly on day 7 and 14 post‐SCI and was restored with GSNO treatment. Following SCI, NFkB expression was increased in the ovarian follicles and the expression was reduced with GSNO administration. The number of terminal deoxynucleotidyl transferase‐mediated biotinylated uridine triphosphate (UTP) nick end labeling positive follicular and luteal cells was increased after SCI. GSNO‐treated animals had significantly fewer apoptotic cells in the ovary.ConclusionSCI‐induced amenorrhea is accompanied by an increase in CX43 expression and a decrease in ERβ expression. SCI animals treated with GSNO resumed the estrous cycle significantly earlier. These results indicate a potential therapeutic value for GSNO in treating amenorrhea among SCI patients. Shunmugavel A, Khan M, Chou PC, and Singh I. Spinal cord injury induced arrest in estrous cycle of rats is ameliorated by S‐nitrosoglutathione: Novel therapeutic agent to treat amenorrhea. J Sex Med 2012;9:148–158.     

Silymarin attenuated mast cell recruitment thereby decreased the expressions of matrix metalloproteinases-2 and 9 in rat liver carcinogenesis

Summary  Liver cancer is the sixth most common cancer worldwide but because of very poor prognosis, it is the third most common cause of death from cancer. There are currently limited therapeutic regimens available for effective treatment of this cancer. Silymarin is a naturally derived polyphenolic antioxidant, is the active constituent in a widely consumed dietary supplement milk thistle (Silybum marianum) extract. Mast cells play an important role in the inflammatory component of a developing neoplasm; they are also a major source for matrix metalloproteinases (MMPs), which are involved in invasion and angiogenesis. In the present study, we investigated whether dietary supplementation of silymarin has any role in mast cell density (MCD) and in the expressions of MMP-2 and MMP-9 in N-nitrosodiethylamine induced (NDEA) liver cancer in Wistar albino male rats. NDEA administered rats showed increased MCD as revealed by toluidine blue staining along with upregulated expressions of MMP-2 and MMP-9. Silymarin treatment inhibited this increase in MCD and downregulated the expressions of MMP-2 and MMP-9 as revealed by Western blotting and immunohistochemistry. In conclusion, silymarin exerted beneficial effects on liver carcinogenesis by attenuating the recruitment of mast cells and thereby decreased the expressions of MMP-2 and MMP-9.     

Ameliorating effect of capsaicin on alterations in lipid metabolism during mice lung carcinoma

Spices and vegetables possess antioxidant activity that can be applied for preservation of lipids and lower lipid peroxidation in biological systems. In the present study, we have investigated the effect of capsaicin on lipid metabolism during benzo(a)pyrene induced lung cancer in Swiss albino mice. Benzo(a)pyrene (50 mg/kg wt) induced lung cancer animals showed abnormal changes in the tissue and serum lipids, lipoproteins and lipid metabolizing enzymes. Treatment with capsaicin (10 mg/kg body wt) remarkably attenuated all the above alterations and restored normalcy. These findings reveal the chemomodulatory potential of capsaicin in attenuating the alterations in lipid metabolism during experimental lung carcinogenesis.     

A Single-Center, Open, Comparative Study of the Effect of Using Self-Monitoring of Blood Glucose to Guide Therapy on Preclinical Atherosclerotic Markers in Type 2 Diabetic Subjects

Background

The aim of our study was to determine the effect of treatment based on preprandial and postprandial self-monitoring of blood glucose (SMBG) on the progression of carotid intima-medial thickness (CIMT) in noninsulin-treated type 2 diabetes mellitus (T2DM) subjects.

Methods

In this 18-month prospective trial, we recruited subjects 18–70 years of age, treated with metformin and sulfonylurea, with a standardized hemoglobin A1c (HbA1c) level ≤9.0%. Subjects were randomized to use of fasting/preprandial (FP) SMBG results to adjust evening medication or use of postprandial (PP) SMBG results to adjust morning medication. The primary end point was change in CIMT; change in HbA1c was a secondary end point.

Results

Of the 300 subjects randomized, 280 (140 in each group) completed all biochemical tests and CIMT analysis. Carotid intima-medial thickness was reduced significantly in PP subjects from 0.78 (±0.15) mm to 0.73 (±0.14) mm (p < 0.005), but no significant CIMT reduction was seen in FP subjects. A significant reduction in HbA1c was also seen in the PP group (p < 0.005) but not in the FP group 1 (p = 0.165). Significant improvements in body mass index (p = 0.038), waist circumference (p < 0.001), systolic blood pressure (p = 0.008), and serum cholesterol (p = 0.02) were also seen in PP subjects but not in FP subjects.

Conclusion

Use of postprandial SMBG data to adjust therapy was associated with a significant regression of carotid intima-medial thickening and a reduction in HbA1c in T2DM, whereas no significant improvement in these parameters was seen in subjects who used fasting/preprandial SMBG data for therapy adjustment.     

Mid-trimester fracture of femur in a normal fetus

We report a case of an intrauterine fracture of the femur detected at routine mid-trimester sonography in an otherwise normal fetus. There was no associated maternal trauma. At birth, callus formation was palpable and confirmed by radiography. Absence of further fractures despite normal childhood activity and other features precluded a diagnosis of skeletal dysplasia. Although such an event is extremely rare, the possibility of an intrauterine origin should be considered in the differential diagnosis of battered baby syndrome presenting with a single fracture.     

Follicular-phase response in two clomiphene-human menopausal gonadotropin regimes for an in vitro fertilization program

Two clomiphene-human menopausal gonadotropin regimes were assessed for our in vitro fertilization and embryo replacement (IVF and ER) program since September 1983. Clomiphene, 50 mg bd, was taken from day 2 for 5 days. Human menopausal gonadotropin (hMG) was given from day 6; for the first regime, 75 IU/day was given for the first 3 days, and for the second, 150 IU/day. The subsequent dosages were dependent on the estradiol response. There were 9 cases for the first regime and 10 cases for the second. The mean number of hMG ampoules given was 16.5 and 19.25, respectively. The number of follicles seen on ultrasound was 3.0±0.5 and 3.4±1.2 (mean±SD), respectively. There was no statistical difference in the estradiol response up to the day of laparoscopic ova recovery for the two regimes. However, a spontaneous luteinizing hormone (LH) surge was observed in 4 of 9 cases in the first group and 6 of 10 cases in the second group. When a comparison was made between cases that had a spontaneous LH surge and cases that were given human chorionic gonadotropin (hCG), there was a higher estradiol level on the day of the laparoscopy in the hCG group with the lower hMG regime (P<0.05). There were no other differences. Our small series shows a 52.6% incidence of spontaneous LH surge with clomiphene-hMG. Hence such stimulated regimes can result in a high proportion of spontaneous LH surges; this may be an index of satisfactory endocrinological control in spite of an increase in the number of follicles.     

Efficient marking of murine long-term repopulating stem cells targeting unseparated marrow cells at low lentiviral vector particle concentration.

HIV-1-derived lentivirus vectors offer unique biological properties for gene delivery to hematopoietic stem cells and, when used at high multiplicities of infection (m.o.i.), permit efficient gene transfer after minimal target cell stimulation. However, such a strategy has been shown to promote multicopy proviral integration, potentially increasing the risk of insertional mutagenesis. To minimize cell manipulation, we targeted unseparated marrow and demonstrated that transduction at an m.o.i. of 1 resulted in up to 12% vector-modified peripheral blood leukocytes and successful repopulation of secondary recipients with vector-marked cells. Real-time PCR showed on average 1.8 proviral integrants per GFP-marked cell. By comparison, a cohort of animals transplanted with cells transduced at m.o.i. of 10 under otherwise unchanged conditions showed up to 45% marking with an average of 7 copies per GFP-expressing cell. Both m.o.i. groups demonstrated sustained proviral expression with stable GFP fluorescence intensity. In summary, we have identified conditions for lentiviral gene transfer involving minimal ex vivo target cell manipulation and have shown that the m.o.i. is a critical determinant of proviral copy number in lentivirus-transduced murine long-term repopulating cells. Thus, gene transfer efficiencies may be limited when single-copy integration is desired and additional strategies such as in vivo selection may be required to improve the frequency of gene-modified cells.     

Management trend and safety of vaginal delivery for term breech fetuses in a tertiary care hospital of Karachi, Pakistan.

AIM: To investigate the safety of vaginal delivery for term breech fetuses in a tertiary-care hospital of Pakistan. METHODS: We reviewed the medical records of all live singleton breech deliveries at or beyond 37 weeks of gestation, at the Aga Khan University Hospital, Karachi, from January 1988 to December 1995. RESULTS: Rate of cesarean section increased from 48% (1988) to 74% (1995). Out of 287 subjects, 158 underwent elective cesarean section while 129 received a trial of labor, 77% of which delivered vaginally. There was no neonatal or maternal death. Compared to babies delivered by emergency or elective cesarean section, those delivered vaginally had significantly more neonatal intensive-care unit admissions (none and 5% versus 13%) and higher rates of birth trauma (none and 0.6% versus 7%). However, there was no significant difference in the Apgar score at 5 minutes and the risk of maternal complications by delivery mode. CONCLUSION: Allowing trial of labor to carefully selected mothers can result in vaginal delivery in 77% of the cases. However, the risk of trauma and neonatal intensive-care unit admissions, among vaginal births may favor the decision of elective cesarean section, unless rigorous pre-delivery assessment and conduct of delivery by adequately trained obstetricians is performed.