Pituitary adenylate cyclase-activating polypeptide causes tyrosine phosphorylation of the epidermal growth factor receptor in lung cancer cells

Pituitary adenylate cyclase-activating polypeptide (PACAP) is an autocrine growth factor for some lung cancer cells. The activated PACAP receptor (PAC1) causes phosphatidylinositol turnover, elevates cAMP, and increases the proliferation of lung cancer cells. PAC1 and epidermal growth factor receptor (EGFR) are present in non-small-cell lung cancer (NSCLC) cells, and the growth of NSCLC cells is inhibited by the PAC1 antagonist PACAP(6-38) and the EGFR tyrosine kinase inhibitor gefitinib. Here, the ability of PACAP to transactivate the EGFR was investigated. Western blot analysis indicated that the addition of PACAP but not the structurally related vasoactive intestinal peptide increased EGFR tyrosine phosphorylation in NCI-H838 or H345 cells. PACAP-27, in a concentration-dependent manner, increased EGFR transactivation 4-fold 2 min after addition to NCI-H838 cells. The ability of 100 nM PACAP-27 to increase EGFR or extracellular signal-regulated kinase tyrosine phosphorylation in NCI-H838 cells was inhibited by PACAP(6-38), gefitinib, 4-amino-5-(4-chlorophenyl)-7-(dimethylethyl)pyrazolo[3,4-d]pyrimidine (PP2; Src inhibitor), (R)-N4-hydroxy-N1-[(S)-2-(1H-indol-3-yl)-1-methylcarbamoyl-ethyl]-2-isobutyl-succinamide (GM6001; matrix metalloprotease inhibitor), or antibody to transforming growth factor α (TGFα). By enzyme-linked immunosorbent assay, PACAP addition to NCI-H838 cells increased TGFα secretion into conditioned media. EGFR transactivation caused by the addition of PACAP to NCI-H838 cells was inhibited by N-acetyl-cysteine (antioxidant), tiron (superoxide scavenger), diphenylene iodonium (NADPH oxidase inhibitor), or 1-[6-[[(17β)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U73122; phospholipase C inhibitor), but not N-[2-[[3-(4-bromophenyl)-2-propenyl]amino]ethyl]-5-isoquinolinesulfonamide (H89; protein kinase A inhibitor). PACAP addition to NCI-H838 cells significantly increased reactive oxygen species, and the increase was inhibited by tiron. The results indicate that PACAP causes transactivation of the EGFR in NSCLC cells in an oxygen-dependent manner that involves phospholipase C but not protein kinase A.     

Parity and perinatal mortality amongst diabetics in a Nigerian Teaching Hospital

The parity and the perinatal mortality of 226 married Nigerian female diabetics, aged 20 to 76 years (mean 47.1 years), and 226 married female nondiabetics matched for age and educational level with the diabetics were studied. There was no statistically significant difference between the diabetics and nondiabetics in terms of primary infertility, irrespective of age of onset of diabetes. In the group with one to four deliveries, the nondiabetics significantly outnumbered the diabetics (P less than 0.001) irrespective of age of onset of diabetes. In the group with seven to nine deliveries, only the diabetics of child-bearing age (P less than 0.01); and in the group with 10 or more deliveries, diabetics significantly outnumbered the nondiabetics irrespective of age of onset of diabetes (P less than 0.01). There was a statistically significant difference between the diabetics and nondiabetics in terms of the overall perinatal mortality (P less than 0.001). However, this difference was not significant in diabetics of childbearing age. In Nigeria, where large families are common and children often born in rapid succession, high parity appears not only to increase the chances of a woman developing diabetes in late life but also in early life. Effective birth control practice may thus help in reducing the incidence of diabetes amongst Nigerian women. Additionally, a programme extending to the rural areas aimed at early detection of diabetes and proper management of the pregnant diabetic by a team of medical personnel with special interest in diabetes will help in reducing the perinatal mortality in Nigerian diabetics.     

Gastric acid hypersecretory states: Recent insights and advances

Gastric acid hypersecretory states are characterized by basal hypersecretion of gastric acid and historically include disorders associated with hypergastrinemia, hyperhistaminemia, and those of unknown etiology. Although gastric acid secretion is infrequently measured, it is important to recognize the role of gastric hypersecretion in the symptoms of these disorders because they share several features of pathogenesis and treatment. In this article, recent important articles reporting insights into their diagnosis, pathogenesis, and treatment are reviewed. Particular attention is paid to Zollinger-Ellison syndrome, because it has the most extreme acid hypersecretion of this group of disorders and because numerous recent articles deal with various aspects of the diagnosis, molecular pathogenesis, and treatment of the gastrinoma itself or the acid hypersecretion. Two new hypersecretory disorders are reviewed: rebound acid hypersecretion after the use of proton pump inhibitors and acid hypersecretion with cysteamine treatment in children with cystinosis.     

Endometriosis: incidence among the Igbos of Nigeria

A retrospective study of the incidence of endometriosis among the Igbos was undertaken. The incidence was 4.3% in patients with pelvic operations. This is the highest incidence ever reported for Nigeria. Differences in educational standards, ethnic habits and improved diagnostic resources of this hospital were the possible influencing factors; 90.8% of the cases were not diagnosed before operation, demonstrating the lack of awareness. Differential diagnostic considerations for menstrual disorders should include endometriosis in this environment.     

Cesarean and postpartum hysterectomy in Enugu, 1973-1986

Obstetric hysterectomies were performed on 163 patients over a period of 13 years out of 56,823 deliveries. Seventy-one percent of the patients received no antenatal care in the index pregnancies. The majority were of high parity. Ruptured uterus was the commonest indication. Inadequate transfusion and late presentation affected the prognosis adversely. Ignorance, availability of suitable maternity care units and uncontrolled reproductive patterns were the main predisposing factors.