Concentrating ability of the kidneys in proteinuric patients

Proteinuria causes damage to renal tubulointerstitium. The study included 50 patients (24 males and 26 females), mean age 46.50?13.08 years, with average endogenous creatinine clearance 87.29?31.17 ml/min. Regarding level of glomerular proteinuria patients were divided into three groups. The first group, with proteinuria less than 0.3 g/24h, included 19 patients (7 male and 12 female), average age 45.12?13.28 years and mean clearance of endogenous creatinine 94.27?34.70 ml/min. The second group, with proteinuria between 0.3 and 3.0 g/24h, comprised 18 patients (8 male and 10 female), mean age 45.39?12.64 years, and with mean clearance of endogenous creatinine 90.07?31.89 ml/min. The third group consisted of 13 patients (9 male and 4 female) with proteinuria values higher than 3,0 g/24h, average age 50.08?13.73 years and mean endogenous creatinine clearance 73.25?20.44 ml/min. In order to assess the concentrating ability of the kidneys we investigated: urine osmolality, osmolar concentration index, fractional osmolar excretion, fractional urea excretion and free water clearance. Results were statistically analyzed using Student, Mann-Whitney U test and (? test. Proteinuria leads to deterioration of concentrating ability of the kidneys.

Drinking and vasopressin release during ventricular infusions of hypertonic solutions

Six dogs were administered third ventricular infusions of artificial cerebrospinal fluid (CSF) (292 mosmol/l) alone or artificial CSF to which neither NaCl, sucrose, glucose, or urea was added to yield a final osmolar concentration of 500 mosmol/l. The volume of water drunk during 45 min of infusion was measured and blood was sampled for determination of plasma vasopressin concentration at 15-min intervals. Artificial CSF made hypertonic by addition of NaCl or sucrose stimulated water intakes of 9.0 +/- 3.2 ml/kg (mean +/- SE) and 7.3 +/- 3.7 ml/kg, respectively. There was no statistical difference in the amounts drunk and the latencies. In contrast, artificial CSF containing glucose, urea, or artificial CSF alone were without effect. Plasma vasopressin concentration increased significantly in response to intraventricular NaCl and sucrose but was not affected by glucose, urea, or artificial CSF alone. These data are compatible with an osmoreceptor mechanism mediating drinking and vasopressin release.

ENERGY-LINKED ULTRASTRUCTURAL TRANSFORMATIONS IN ISOLATED LIVER MITOCHONDRIA AND MITOPLASTS

An investigation was carried out in which microsamples of isolated rat liver mitochondria and freshly prepared mitoplasts in defined energy states were freeze-cleaved. Parallel microsamples were fixed with osmium tetroxide and with glutaraldehyde followed by osmium tetroxide as previously used in this laboratory for the preservation of energy-linked mitochondrial configurations. The details of the orthodox configuration of energized mitochondria and the condensed configuration of de-energized mitochondria, as revealed previously by chemical fixation, are confirmed in this report for nonfixed, freeze-cleaved mitochondria. The precise agreement in preservation of configuration obtained by the physical fixation of rapid freezing and by chemical fixation establishes unequivocally that mitochondria undergo energy-linked ultrastructural transformation between the condensed and the orthodox configurations which are thus natural structural states related to the metabolic activity of the mitochondrion. Configurations observed by freeze-cleaving and by chemical fixation reveal that mitoplasts also undergo a specific and dramatic ultrastructural transformation with the induction of oxidative phosphorylation. The transformation appears to be isovolumetric and therefore is thought to be mediated through energized conformational activity in the surface electron-transport membrane of the mitoplast. Passively swollen, spherical, osmotically active mitoplasts could not be fixed rapidly enough by chemical fixatives as normally used without altering the spherical form. In this special case preservation of configurational form required rapid freezing or chemical fixatives of low osmolar concentration.

ION-INDUCED ULTRASTRUCTURAL TRANSFORMATIONS IN ISOLATED MITOCHONDRIA

The energized uptake of low levels of Ca2+ in the presence and absence of phosphate by isolated rat liver mitochondria, and the perturbation effected by this activity on ultrastructural and metabolic parameters of mitochondria have been investigated. In the presence of phosphate, low levels of Ca2+ are taken up by mitochondria and result in various degrees of ultrastructural expansion of the inner mitochondrial compartment. This indicates that low levels of Ca2+ in the presence of phosphate, are accumulated in an osmotically active form into the water phase of the inner compartment. The first clearly observable quantitative increase in the volume of the inner compartment occurs after the accumulation of 100 nmoles Ca2+/mg protein. An accumulation of 150–200 nmoles Ca2+/mg protein, which is equivalent to the osmolar concentration of endogenous K+, is required to effect a doubling of the volume of the inner compartment. This degree of osmotic perturbation occurs as mitochondria transform from a condensed to an orthodox conformation. The osmotically induced orthodox conformation differs from the mechanochemically induced orthodox conformation previously described, in that its development is concomitant with a marked decrease in acceptor control and oxidative phosphorylation efficiency and it fails to transform to a condensed conformation in response to addition of ADP. In the absence of added phosphate, a maximum of 190 nmoles Ca2+/mg protein was found to be taken up by mitochondria (state 6). Ca2+ is apparently bound under state 6 conditions since the uptake does not effect an ultrastructural expansion of the inner compartment. Phosphate added after state 6 Ca2+ binding, however, results in an immediate ultrastructural expansion of the inner compartment. The addition of phosphate to mitochondria in the absence of exogenous Ca2- fails to effect an osmotic ultrastructural transformation. Under state 6 conditions, the binding of between 40 and 190 nmoles Ca2+/mg protein results in the formation of dense matrix inclusions which appear to be composed of tightly packed, concentrically oriented membranes. Under conditions in which the bound Ca2+ is subsequently released, there is a concomitant loss in the density of these matrix inclusions, leaving behind morphologically distinct membrane whorls in the mitochondrial matrix.

Influence of osmolarity of perfusate on contractility of mammalian myocardium

The effect of changes in the osmolarity of the perfusing fluid on strength and time course of myocardial contraction was studied in cat papillary muscles and atrial strips. Osmolar concentration was varied by adding up to 750 mm sucrose or mannitol to a slightly hypoosmolar solution, leaving molar concentrations of the original solutes unchanged. Optimum osmolarity for tension development by papillary muscles was close to that of serum (330 mosmol/ liter), but for atrial muscles was 150 mosmol/liter higher. Osmolarity changes apparently influence contractility by altering the intracellular water concentration. Increases of osmolarity up to the optimum augment tension development by increasing the degree of activation of the contractile elements. This may be due to increased concentration of calcium in a superficial area of the fiber. Increases of osmolar concentration above the optimum lower developed tension, probably by reducing the intrinsic speed of the muscle. Tension development in response to external stimuli is abolished by raising osmolarity to three times that of serum (1 osmol/liter). Spontaneous contractions cease in solutions of twice normal osmolar concentration.

Contents and distributions of potassium, sodium, and chloride in uterine smooth muscle

For the immature uterus the water, potassium, sodium, and chloride (per kg wet tissue) are 838 g, 101 mEq, 87 mEq, and 67 mEq, respectively; for isolated myometrium under estrogen domination they are 799 g, 109 mEq, 79 mEq, and 67 mEq, respectively; for isolated myometrium under progesterone domination they are 792 g, 111 mEq, 83 mEq, and 72 mEq, respectively. Potassium contents are higher than those reported previously by other investigators, owing to a technique of preparation that avoided leaching of K from the tissues. Extracellular spaces estimated by distributions of inulin are 327 ml/kg for immature uterus, 322 ml/kg for estrogen-dominated myometrium, and 312 ml/kg for progesterone-dominated uterus. There is little statistically significant difference between extracellular spaces or ion content of the different hormonally affected uterus or myometrium. In estrogen-dominated myometrium, 14 mEq/kg of K and 29 mEq/kg of Na are unextractable in neutral isotonic sucrose. In progesterone-dominated myometrium, they are 4 and 9 mEq/kg, respectively. After correction for unextractable fractions, the sum of intracellular Na, K, and Cl in estrogen-dominated myometrium is in fair agreement with the total osmolar concentration of serum, but in progesterone-dominated myometrium it is still greater than the total osmolar concentration of serum.

Net absorption of water, chloride and hexose from the intestine of dogs

Hexose and/or NaCl solutions were perfused at about 100 cm H2O pressure through small intestinal loops in unanesthetized dogs. The rate of glucose absorption increased in curvilinear fashion as the glucose concentration of the infusate ranged from 1% to 30% and did not differ between jejunal and ileal loops. Net chloride secretion rates were independent of perfusate hexose concentrations and were greater for jejunal than for ileal loops when nonchloride solutions were infused. Net chloride absorption rates increased with infusate concentrations ranging from 0.2% to 1.8% NaCl, and were greater for ileal than for jejunal loops. However, this difference may be due to the greater chloride secretion of jejunal loops. The curvilinear relationship between moles of glucose or chloride absorbed and lumen concentrations of these substances was rectified by plotting absorption rates against log concentration. The resulting Δ mm absorbed per hour/Δ log mm per liter concentration of the perfusate averaged 10.1 and 8.7 for chloride and glucose, respectively, in 6 dogs. Net fluid absorption rate decreased in curvilinear fashion with increasing perfusate osmolar concentration when NaCl or hexose was given. Net fluid absorption at given osmolar perfusate concentrations was greater from NaCl than from glucose or sorbose solutions.