Comparison of the in vitro effects of K+ channel modulators on detrusor and portal vein strips from guinea pigs.

The effects of K+ channel openers and blockers on smooth muscles of vascular and nonvascular origin from guinea pigs have been investigated. Cromakalim, pinacidil, nicorandil and minoxidil sulfate all abolished the spontaneous myogenic activity of the guinea pig portal vein and the KCl-evoked activity of detrusor strips with the same rank order of ptoency. Whereas both apamin and charybdotoxin stimulated myogenic activity of the detrusor strips, they produced insignificant effects on spontaneously active portal vein strips and failed to antagonize the mechanoinhibitory effects of cromakalim in the two tissues. Glibenclamide, on the other hand, only stimulated the myogenic activity of portal vein strips but antagonized the mechanoinhibitory effects of cromakalim, pinacidil, nicorandil and minoxidil sulfate in both tissues. Rubidium, at millimolar concentrations, stimulated the myogenic activity, and antagonized the actions of cromakalim in both tissues. The data indicate that there are definite functional dissimilarities as exhibited by the differential response of the two tissues to K+ channel modulators. These findings may be exploited in the design of new drugs with tissue selectivity.     

MRI and proton-NMR relaxation times in diagnosis and therapeutic monitoring of squamous cell carcinoma

The potential application of MRI and proton nuclear magnetic resonance (NMR) relaxation times to predict tumor growth and tumor response to therapy is investigated in 91 patients with various head and neck tumors. Of the 91 patients 38 underwent surgery and 53 underwent combined modality treatment (radiochemotherapy; RCT). The MRI morphology parameters and proton-NMR relaxation times before, during, and after therapy were evaluated. The spin-lattice T1 relaxation time of squamous cell carcinoma (SCC) primary tumors is 815 ±128 ms. The following is the SCC primary tumor's behavior during therapy: Following the first RCT course 21 patients showed a complete tumor remission by volumetric morphological, and relaxometric parameters due to normalization; 32 patients showed a significant reduction in T1 relaxation time in the primary SCC tumor region (712 ± 117 ms); 19 showed residual tumors and 13 showed reactive inflammation in biopsy. In 24 cases a morphological normalization was determined following the second RCT course; in 29 cases MR morphology showed residual signal-intensity pathology and an elevation of T1-time values (787 ± 139 ms), but histology verified residual tumors in only 6 of these patients. Reactive edema and inflammation overlies MRI's morphology and relaxometry parameters in further controls. The histological verification shows a spin-lattice T1 relaxation time of 549 ± 181 ms for hyperplastic lymph nodes, 924 ± 116 ms for malignant SCC lymph nodes, and 854 ± 23 ms for inflammation. The sensitivity of the spin lattice relaxation time is 82%, and the specificity is 93%. The negative predictive value is 85% and the positive predictive value is 93%. The T1 relaxation time of hypothetical malignant lymph nodes changes during combined modality treatment: Following the first RCT course in residual lymph nodes the spin-lattice relaxation time is reduced significantly (P < 0.01; T1 = 785 ± 116 ms). After the second course the reduction is more pronounced (P < 0.01; T1 = 731 ± 71 ms), reaching values of hyperplastic lymph nodes expressing a normalization. We conclude that the spin-lattice relaxation time improves lymph nodes classification, and the T1 relaxation time is useful as a predictive assay indicating favorable therapeutic changes.     

Continuous physical activity promotes healthy ageing

The growth in the prevalence of chronic diseases of civilization is of concern. In Croatia, diseases of the circulatory system are the main cause of hospitalization amongst people aged >65 and the main cause of death for two thirds of those aged >65. Continuous physical activity in older people stands out as an important factor in the prevention of chronic diseases of civilization, particularly diseases of the circulatory system, but also for other health problems. A survey on the extent of physical activity amongst older people aged >65 carried out in Zagreb (N=449, Croatian Health Survey/2003; CROCAN Project) has shown that 42.8% were physically inactive, whilst only 19.1% were physically active on a daily basis. Physical activity, two to three times per week, which is recommended by WHO, was undertaken by 11.6% of those aged >65. These gerontologic health indicators show that the Programme of preventative measures is insufficiently applied amongst the elderly. This Programme includes primarily kinesiologic measures adapted for the elderly as developed in the study. It is important to ensure that the Programme of continuous physical activity is applied amonst the elderly to promote active healthy ageing. The type of physical activity, its intensity and frequency should be adapted to each individual's health status, their interests, physical condition and the extent of any previous experiences of physical activity.Thus, professional guidance, consultation with kinesiologists for the elderly and general practitioners as well as the collaboration with other medical specialists are necessary.     

Metabolic Fate of [14C]Cefamandole, a Parenteral Cephalosporin Antibiotic, in Rats and Dogs

The biotransformation of the parenterally effective cephalosporin antibiotic cefamandole nafate (I) has been studied in rats and dogs. After rapid in vivo hydrolysis of the nafate pharmaceutical form to cefamandole (II), the antibiotic was found to be very resistant to metabolic degradation in both species. In dogs, cefamandole escaped metabolism and was eliminated as unaltered antibiotic almost exclusively by renal excretion. In rats, cefamandole was somewhat labile to metabolism; however, a major portion of the administered antibiotic was eliminated unchanged principally by renal excretion.     

Drainage of the middle ear

Otitis media with effusion occurs very frequently in childhood and usually heals without therapy. The condition is thought to be due to a higher susceptibility to infections of the upper respiratory tract and the fact that the Eustachian tube is not yet functioning perfectly at that age. Many authors explain this astonishingly high rate of spontaneous recoveries by tube malfunction alone, never even considering a middle ear clearance system. It is known from the paranasal sinuses that the cavities are regularly and continually cleaned according to very precise rules. In in-vivo experiments with guinea pigs the author proved that there is an obvious similarity between the paranasal sinus and the middle ear as far as the clearance system is concerned. By applying tracer substances to the middle ear mucosa the usual drainage pathways out of the middle ear into the Eustachian tube, and the different rates of drainage were very precisely defined.     

Bumetanide stimulation of sodium permeability of the apical membrane of toad urinary bladder

The effects of bumetanide on Na transport in the isolated toad urinary bladder were investigated. When applied to the serosal side, this loop diuretic inhibited Na transport. By contrast, when applied to the mucosal side, it stimulated Na transport by increasing the apical Na permeability. These dual effects of bumetanide were also observed with the loop diuretic furosemide. The mucosal action of bumetanide was attributable to release of Na self-inhibition, as evidenced by its dependency on mucosal Na concentration and its interaction with another apical Na permeability stimulator, p-chloromercuriphenyl sulfonate. The stimulatory action of bumetanide was not reduced by the natriferic effect of antidiuretic hormone, but it was totally blockable by the epithelial Na channel blocker amiloride. Bumetanide, however, caused a leftward shift of the concentration-response curve of amiloride on Na current as predicted from its effect on Na self-inhibition. This stimulatory activity of bumetanide and furosemide as demonstrated in the in vitro isolated amphibian epithelia suggests that these loop diuretics also have the potential to stimulate Na transport at the distal portion of the mammalian nephron. Thus, this property of these diuretics might be one of the factors contributing to the observation of increased Na reabsorption along the distal tubule after in vivo administration of furosemide and piretanide as reported in some micropuncture studies.