The effect of selective mass-chemotherapy with praziquantel at a dose of 60 mg/kg a day on the annual incidence of Schistosoma japonicum infection was examined by a follow-up study of 1,800 school children enrolled at 9 primary schools at Dagami Area, Leyte, Philippines. The incidence rates before mass-chemotherapy were 22.2, 24.2, 26.9, 9.6 and 28.4% in a period from school year (SY) 1975/76 to 1979/80, respectively, where the incidence of 9.6% in SY 1978/79 was probably due to extraordinary drought in the previous year. Egg positives including village people were treated and the numbers treated yearly were 22, 943, 273, 300 and 341 from SY 1978/79 to SY 1982/83, respectively. The incidence was reduced drastically as early as one year following the start of mass-chemotherapy, i.e., 8.4, no survey, 6.8 and 15.4%, from SY 1980/81 to SY 1983/84, respectively, and which demonstrated the efficacy of mass-chemotherapy on reduction of transmission.
The mechanism for myocardial automaticity may differ among different regions of the heart. In this study, we performed fluorescent ion measurements in cardiomyocytes from the sinoatrial node (SAN), the orthotopic pacemaker, and the pulmonary vein (PV), a potential ectopic pacemaker which may cause atrial fibrillation, focusing on the role of the Na+/Ca2+ exchanger (NCX). Isolated cardiomyocytes from the guinea pig PV and SAN showing automaticity were loaded with the Ca2+ indicators Fluo-4 or Indo-1 for high-speed Ca2+ imaging. Inhibition of NCX either by SEA0400 or by low Na+ solution decreased the Ca2+ transient frequency in PV, but not in SAN. The basal cytoplasmic Ca2+ concentration, as well as the number of Ca2+ sparks between Ca2+ transients, were slightly higher in PV than in SAN. Intracellular Na+ concentration, measured by a Na+ indicator SBFI, was not different between PV and SAN. The equilibrium potential of NCX (ENCX) was estimated to be less negative in PV than in SAN. In conclusion, NCX is involved in spontaneous activity in PV, but not in SAN. This is probably because the less negative ENCX and the more negative voltage range for diastolic depolarization in the PV cause a larger driving force for NCX. In the SAN, whose diastolic depolarization largely overlaps with the ENCX, the role of NCX in automaticity is limited.
Aquaporin-8 (AQP8), a member of the aquaporin water channel family, is expressed in various tissue and cells, including liver, testis, and pancreas. AQP8 appears to have functions on the plasma membrane and/or on the mitochondrial inner membrane. Mitochondrial AQP8 with permeability for water, H2O2 and NH3 has been expected to have important role in various cells, but its information is limited to a few tissues and cells including liver and kidney. In the present study, we found that AQP8 was expressed in the mitochondria in mouse adipose tissues and 3T3-L1 preadipocytes, and investigated its role by suppressing its gene expression.AQP8-knocked down (shAQP8) cells were established using a vector expressing short hairpin RNA. Cellular localization of AQP8 was examined by western blotting and immunocytochemistry. Mitochondrial function was assessed by measuring mitochondrial membrane potential, oxygen consumption and ATP level measurements.In 3T3-L1 cells, AQP8 was expressed in the mitochondria. In shAQP8 cells, mRNA and protein levels of AQP8 were decreased by about 75%. The shAQP8 showed reduced activities of complex IV and ATP synthase; it is probable that the impaired mitochondrial water handling in shAQP8 caused suppression of the electron transport and ADP phosphorylation through inhibition of the two steps which yield water. The reduced activities of the last two steps of oxidative phosphorylation in shAQP8 cause low routine and maximum capacity of respiration and mitochondrial hyperpolarization.Mitochondrial AQP8 contributes to mitochondrial respiratory function probably through maintenance of water homeostasis.The AQP8-knocked down cells we established provides a model system for the studies on the relationships between water homeostasis and mitochondrial function.
We examined the breath test using 13C-dipeptide for diagnosis of exocrine pancreatic insufficiency. We performed the breath test to both healthy persons (n = 14) and patients who have exocrine pancreatic insufficiency (n = 13). We gave Benzoyl-L-Tyrosyl- [l-13C]Alanine (0.3g) solution to both two groups, and expired gasses were obtained every 10 minutes until 90 minutes, after that every 30 minutes until 240 minutes. We analyzed expired gasses, and evaluated the ratio of 13CO2 to 12CO2 (‰).We calculated 3 parameters, [the peak value of the ratio (‰), the time reaching the peak value (minutes), and the 13C-cumulative dose (%)]. There were statistical significances in each 3 parameters. Meanwhile, we did the same test in other patients who had compensated chronic pancreatitis, diabetes, and chronic renal failure. But, there was no statistical significance in their patients compared with healthy persons. These results showed that the breath test using Benzoyl-L-Tyrosyl-[l-13C]Alanine is useful for diagnosing pancreatic exocrine insufficiency.
The effects of thirteen Vaughn Williams class I antiarrhythmic drugs on the α1-adrenergic receptor-mediated contraction were examined in thoracic aorta tissue preparations isolated from the guinea pig. Cibenzoline, quinidine, aprindine, and ranolazine, as well as prazosin, inhibited the phenylephrine-induced contraction with pA2 values of 5.64, 5.59, 5.61, 5.08, and 8.50, respectively, but not prostaglandin F2α-induced. These drugs reduced the staining of the smooth muscle layer by fluorescent prazosin. Propafenone inhibited the phenylephrine-induced contraction with an apparent pA2 value of 5.31 and reduced the staining by fluorescent prazosin, but also inhibited the prostaglandin F2α-induced contraction. Other class I antiarrhythmic drugs, disopyramide, pirmenol, procainamide, lidocaine, mexiletine, flecainide, pilsicainide, and GS-458967, affected neither the contraction by phenylephrine nor the fluorescent staining by prazosin. These results indicate that among the class I antiarrhythmic drugs, cibenzoline, aprindine, and propafenone, as well as quinidine and ranolazine, have α1-adrenoceptor-blocking activity at therapeutically relevant concentrations.
