Response to repeated frusemide administration on low chloride and low sodium intake in the rat

In animals on a normal NaCl intake despite the repeated administration of a diuretic Cl and Na excretion return to baseline values after initial Cl and Na loss. In order to delineate whether this apparent resistance is consequent primarily on a decreased effect of the diuretic, or compensatory Cl and Na reabsorption when the diuretic is not acting, rats were injected with frusemide (1.5 mg twice a day intraperitoneally for 4 days) while on diets differing in Cl and Na content. On a normal NaCl diet Cl and Na excretion increased on day 1 and subsequently returned to baseline. On a low NaCl diet Cl and Na excretion remained above baseline on all 4 days, thereby demonstrating that frusemide continues to promote daily Cl and Na loss. On a low Cl-normal Na intake Na excretion returned to baseline after day 1, while Cl excretion remained above baseline on all 4 days. The increase in K and net acid excretion was highest in these studies. On a low Na-normal Cl intake Cl excretion returned to baseline after day 2, while Na excretion exceeded baseline on all 4 days. Daily K excretion increased least and net acid excretion decreased in these studies. Hourly data on all four diets indicate that frusemide always has an acute effect to promote both Cl and Na excretion. In the recovery period Cl or Na reabsorption is enhanced when the respective ion is available. The apparent resistance to daily frusemide administration on a normal NaCl intake is primarily consequent on enhanced reabsorption balancing the chloriuretic and natriuretic effects. Daily changes in K and net acid excretion are also determined, in part, by these opposing effects.     

The effect of bleomycin administered in combination with hyperthermia on a C3H mouse fibrosarcoma

The effect of bleomycin (BLM) on a murine fibrosarcoma, FSa-II, was investigated at elevated temperatures. Animals were C3Hf/Sed mice derived from our defined flora mouse colony. Single-cell suspensions of the tumour were transplanted into the murine foot. Tumours with an average diameter of 4 mm were treated in a water bath where a desired temperature was maintained. Some animal groups received an intraperitoneal injection of glucose 60 min before hyperthermia to reduce tumour tissue pH. Hyperthermia was given for 60 min at 41.5 degrees C, 30 min at 43.5 degrees C, or 60 min at 43.5 degrees C, and tumour growth (TG) time to reach 1000 mm3 was studied. BLM treatment at 41.5 degrees C for 60 min prolonged the TG time compared to BLM treatment at a room temperature. The identical prolongation was observed following BLM treatment given at 43.5 degrees C for 30 min, although the growth prolongation was greater following BLM treatment given at 43.5 degrees C for 60 min than the other two treatments. This greater prolongation is probably attributable to an additive effect; namely hyperthermia of 43.5 degrees C for 60 min induces substantial lethal damage by itself while the other two heat treatments do not induce significant damage. It is interesting to note that this kind of enhancement was observed at a low temperature of 41.5 degrees C. A glucose injection before BLM and hyperthermia treatments further enhanced tumour response. These observations agree with our previous observations following in vitro treatments of the same tumour cells, and indicate that BLM is a good drug to be combined with hyperthermia.     

A histologically visible representation of the fingers and palm in primate area 3b and its immutability following long-term deafferentations

An isomorph of the glabrous hand is visible in primary somato-sensory cortex (area 3b) of owl monkeys in brain sections cut parallel to the surface and stained for myelin. A mediolateral row of five ovals, separated by myelin-light septa, represents digits and corresponds precisely with cortical sites activated by light touch on individual digits in microelectrode recordings. A number of caudal ovals relate to pads of the palm. A more distinct septum separates the hand from the more lateral face representation. Within the face representation, two large myelin-dense ovals can be identified that are activated by the upper or lower face in a caudo-rostral sequence. Accidental finger loss or dorsal column section, deafferentations that result in reorganization of the physiological map in area 3b, do not alter the morphological map. The proportions for each digit and palm in the morphological map do not vary across normal and deafferented animals. Similar isomorphs were also seen in area 3b of squirrel and macaque monkeys. We conclude that the anatomical isomorph for the body surface representation in area 3b is a reliable reflection of normal cortical organization and may be a common feature of the primate area 3b. The isomorph can provide a reference in studies of somatotopic reorganization.      

A serotonin hypothesis of panic disorder

Despite numerous animal studies indicating an important role of serotonin (5-HT) in anxiety, 5-HT's function in the regulation of human anxiety has hardly been studied. Recent clinical studies suggest an involvement of 5-HT systems in panic disorder. This paper will briefly review the pertinent data on 5-HT and panic disorder and propose a specific hypothesis on 5-HT abnormalities in that disorder.     

T2 values in the human brain: comparison with quantitative assays of iron and ferritin

Magnetic resonance (MR) imaging with a whole-body imager was performed in 10 fresh, unfixed whole human brains selected randomly from cadavers. All subjects were neurologically intact before death. T2 time constants were measured within the caudate nucleus, putamen, globus pallidus, cortical gray matter, subcortical white matter, and optic radiation. These regions were then excised, and T2 values were measured again with a 1.5-T MR spectrometer. Quantitative assays of iron, ferritin, and protein from these areas were then performed. Iron concentration varied significantly among brain regions, whereas ferritin and protein concentrations were constant among brain regions and among individuals. Neither iron nor ferritin concentration showed any consistent correlation with T2 values. Histologic examination of brain micro-sections with iron- and ferritin-specific stains of demonstrated poor correlation with biochemical assays of ferritin and iron concentrations. Results indicate that T2 values correlate poorly with iron and ferritin concentrations found in neurologically intact brains.