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Biomedical subjects

A J Merola

Publications and source records attributed to A J Merola.

At least 37 records · Page 2Linked to original sources
PubMed1985

Responses of the normal rat kidney to sequential ischemic events.

UNLABELLED: This study was undertaken to help define how one episode of renal ischemia, insufficient to cause acute renal failure, influences the susceptibility of the kidney to a second more severe ischemic event. Female Sprague-Dawley rats underwent either 15 min of bilateral renal artery occlusion (RAO) or sham RAO. They were subjected 30 min, 3.5 h, or 24 h later to 25 min of RAO. Renal function (GFR, BUN, creatinine), histology, and adenine nucleotide concentrations were compared before and after the 25-min ischemic event. Only the rats with a 30-min hiatus between the 15- and 25-min bouts of RAO had significantly worse renal failure than controls subjected to a single 25-min ischemic event. Three findings were noted only in the rats with increased susceptibility: tubular cell swelling and luminal membrane injury prior to 25 min of RAO and a relative failure of ATP formation immediately following 25 min of RAO. Susceptibility to 25 min of RAO did not correlate with preischemia ATP content. CONCLUSION: prior mild ischemic injury transiently lowers renal resistance to a second ischemic event. Normal resistance is rapidly restored once improvements in prior cell membrane injury, cell volume regulation, and cellular energetics occur. However, resistance to additional ischemia can be normal despite persisting depressions in renal ATP content.

Acute Kidney Injury↗
PubMed1985

Effect of exercise training on antioxidant enzymes and cardiotoxicity of doxorubicin.

The purpose of this study was to correlate the exercise-induced changes of oxidant stress enzymes with possible modification of the response to the putative oxidant stressor doxorubicin. Enzymatic and histological changes were studied in mice placed on a 21-wk swim training program (1 h/day, 5 days/wk) with and without anthracycline administration. Doxorubicin (4 mg/kg) was administered intravenously through a tail vein on 10 separate days over a 7-wk period (twice weekly during weeks 10, 11, 14, 15, and 16). Blood, liver, and heart levels of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GP) were measured following the 9th and 21st wk. Myocardial histomorphological observations were made by light microscopy after 21 wk. Following 9 wk of training swim-trained animals had significantly elevated levels of CAT, SOD, and GP in blood, as well as elevated GP in liver. After 21 wk, trained animals, regardless of drug status, had elevated blood CAT and SOD activity and increased liver CAT and GP. Training also produced increases in blood GP, liver SOD, and heart CAT; however, in conjunction with doxorubicin these changes were not seen. The degree of cardiotoxicity was significantly greater in the sedentary drug-treated animals than in the swim-trained drug-treated animals. The results suggest a correlation between antioxidant enzyme levels in blood and liver and the degree of damage caused by an anthracycline drug. It was concluded that exercise ameliorates severe toxic damage caused by doxorubicin administration, possibly by increasing enzymes that combat free radical damage.

Animals↗
PubMed1985

Prevention of bedrest-induced physical deconditioning by daily dobutamine infusions. Implications for drug-induced physical conditioning.

The effects of intermittent infusions of dobutamine were studied in young normal male subjects during a period of bedrest deconditioning to determine whether this synthetic catechol affects physical conditioning processes in humans. 24 volunteers were placed at bedrest and randomized to daily 2-h treatments of saline infusions (control), dobutamine infusions, or maintenance exercise (control). Exercise, hemodynamic, and metabolic studies were performed at base line and at the termination of the 3-wk treatment period. Maximal exercise (duration, oxygen consumption, and workload) fell for the saline group and remained unchanged for the dobutamine and exercise groups. Hemodynamics during exercise were maintained the same as pretreatment base line for the dobutamine and exercise groups, whereas stroke volume and cardiac output dropped and heart rate rose for the saline group. The metabolic profile showed an increased blood lactate response at rest and during submaximal exercise after 3 wk of bedrest for the saline group, and essentially no change for the exercise and the dobutamine groups. Extraction of oxygen across the exercising lower limb rose for the dobutamine group, as did the activity of the skeletal muscle oxidative enzymes, citrate synthetase, and succinate dehydrogenase. In contrast to the exercise control group, the saline and dobutamine groups developed orthostatic hypotension, tachycardia, and accentuation of the renin-aldosterone response over the 3-wk treatment period; for the saline group, this is best explained by the observed fall in blood volume and for the dobutamine group, by the blunting of vascular vasoconstrictive responses. During a period of bedrest deconditioning in humans, infusions of dobutamine maintain many of the physiologic expressions of physical conditioning.

Adult↗
PubMed1985

Effects of mannitol on the postischemic kidney. Biochemical, functional, and morphologic assessments.

UNLABELLED: To determine the effects of mannitol on the postischemic kidney rats were subjected to 25 minutes of renal artery occlusion and immediately after vascular clamp release they received a 2-ml intravenous mannitol bolus (20%). Equimolar urea-injected rats and sham-injected rats served as controls. Postischemic renal blood flow, tubular metabolic work (renal O2 consumption), adenine nucleotide pools, renal oxidant stress (tissue glutathione, malondialdehyde levels), and tubular cell/mitochondrial swelling (histomorphometry) were assessed at variable times during the early vascular reflow period (15 to 60 minutes). The severity of acute renal failure was determined by serial blood urea nitrogen and serum creatinine studies (24, 48 hours), and by renal histology (48 hours). Mannitol increased postischemic renal blood flow (2-fold), renal O2 consumptions (3-fold), and urine flow compared to urea-injected and sham-injected controls. Postischemic glutathione levels were equally depressed (reduced 33%) in all three treatment groups. Malondialdehyde did not rise. Mannitol significantly lowered total adenine nucleotide content without changing ATP at 15 minutes post renal artery occlusion. At 60 minutes post renal artery occlusion, mannitol- and urea-treated groups had comparable ATP levels, 25% higher than the noninjected controls. Mannitol and urea induced comparable decrements in proximal tubular cell swelling, returning cell volumes to normal values. However, mitochondrial swelling was unabated. Mannitol and urea caused significant and nearly identical degrees of functional and morphologic amelioration of renal injury. CONCLUSIONS: Mannitol administered after renal ischemia ameliorates both functional and morphologic aspects of acute tubular injury despite dramatically increasing tubular aerobic work. This protection appears not to be due to early postischemic improvements in adenine nucleotide content, to increased renal blood flow, to increased urine flow, or to a lessening of oxidant stress. The data are consistent with the view that protection results from acute hypertonic solute loading which either directly or indirectly decreases tubular cell but not mitochondrial swelling.

Acute Kidney Injury↗
PubMed1985

Effects of immediate blood flow enhancement on the postischemic kidney: functional, morphologic, and biochemical assessments.

Our purpose was to assess the influence of blood flow enhancement to the immediate postischemic kidney on tubular cell energetics and on the severity of the resulting ischemic acute renal failure (IARF). Female Sprague-Dawley rats were subjected to 40 minutes of bilateral renal artery occlusion (RAO). Half of the rats received a 5% body weight infusion of iso-oncotic saline solution (IOS; over 50 minutes) to acutely increase renal blood flow (RBF) immediately after vascular clamp release. The remaining half of the rats served as controls. The short-term effects (0 to 1 hour after vascular reflow) of IOS infusion on RBF, clearance iothalamate sodium (Cioth), urine Na excretion (UNaE), urine flow rate, tubular metabolic work (renal oxygen consumption, Qo2), adenine nucleotide concentrations, and renal histologic findings were assessed. The severity of the IARF (Cioth histologic findings) was also compared between the IOS-treated and the control groups 24 hours later. Postischemic (0 to 1 hour) RBF in control IARF rats and IOS-treated IARF rats was 2.3 +/- 0.3 and 13.6 +/- 0.4 ml/min, respectively (P less than 0.01) (normal RBF 6.1 +/- 0.4 ml/min). At 0 to 1 hour after reflow IOS-treated IARF rats had significantly higher Cioth (13 X), UNaE (18 X), urine flow (18 X), and Qo2 (4 X) than the control IARF group. Despite the fourfold increase in aerobic tubular work induced by IOS infusion, renal adenosine triphosphate (ATP) content did not decrease. At 24 hours after vascular reflow the severity of IARF was the same in the control and IOS-treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1984

Prostaglandin response in the exercise conditioned rat.

Thrombin- and collagen-induced thromboxane A2 (TxA2) production were significantly reduced in washed platelets from exercise-trained rats as compared to sedentary controls. No consistant differences were found in the synthesis of prostacyclin (PGI2) from endogenous arachidonate in strips of aorta. Isolated hearts perfused by the "Langendorff" method respond to bolus injections of PGI2 with a decreased perfusion pressure. Hearts from exercised-trained animals were more responsive than those from sedentary animals to the vasodilating effects of PGI2. The increased ratio of PGI2/TxA2 and the increased responsiveness of the coronary vasculature to PGI2 seen in the trained rats may provide protection from cardiovascular disease.

6-Ketoprostaglandin F1 alpha↗
PubMed1982

Influence of dietary vitamin E on platelet thromboxane A2 and vascular prostacyclin I2 in rabbit.

Rabbits were maintained on vitamin E-deficient and vitamin E-supplemented diets. Thrombin- and collagen-induced thromboxane A2 production were significantly elevated in vitamin E-deficient platelets. Conversion of arachidonic acid to platelet thromboxane A2 was unchanged between the two groups of animals. Prostacyclin I2 production in the aortas from vitamin E-deficient rabbits was significantly elevated.

6-Ketoprostaglandin F1 alpha↗
PubMed1982

Alterations of the prostacyclin-thromboxane ratio in streptozotocin induced diabetic rats.

Thrombin induced thromboxane A2 and prostaglandin E2 production were significantly increased in platelets of streptozotocin induced diabetic rats as compared to non-diabetic control rats, while collagen induced thromboxane A2 production was decreased. Using exogenous arachidonic acid, prostaglandin E2 production, but not thromboxane A2 production, was increased in platelets from streptozotocin treated animals. Prostacyclin production in the diabetic aorta was significantly lowered; however, control levels of prostacyclin production resulted after incubation of the tissue with dipyridamole. Diabetic animals demonstrated a fivefold decrease in the endogenous arterial prostacyclin/platelet thromboxane A2 ration when thrombin or ADP was used to induce thromboxane A2 production. This elevated ratio could be a contributing factor to the vascular complications of diabetes. Dipyridamole, due to its ability to partially normalize this ratio, may be useful as a therapeutic agent in this and related vascular diseases.

Animals↗
PubMed1982

Enzyme adaptations in rat skeletal muscle after two intensities of treadmill training.

The effects of high intensity, short duration chronic exercise (HSD, N = 9) and low intensity, long duration chronic exercise (LLD, N = 9) on the selected enzyme activities of three muscles of rats were studied. After 12 wk of treadmill training, the LLD group showed 15-23% decreases in lactate dehydrogenase activity in all muscles (P less than 0.05), while succinic oxidase activity increased in the soleus (49%) and the vastus lateralis profundus (42%) (P less than 0.05). No change in creatine kinase activity was found in either group. The HSD group showed no change in lactate dehydrogenase activity; however, phosphofructokinase activity increased (greater than 50%) in both of the fast-twitch muscles (P less than 0.01), while only the vastus lateralis superficialis showed increased succinic oxidase activity (30-40%) (P less than 0.05). Following training no difference was observed in mean heart weights; however, the mean body weight of the sedentary control group (SC, N = 9) was greater than both exercise groups (P less than 0.05). No difference was observed between the exercise groups. The mean heart weight/body weight ratios were significantly different between all groups (P less than 0.01). These results indicated that the HSD group selectively increased its glycolytic power, while the LLD group increased only its oxidative ability. Furthermore, both exercise groups exhibited less gains in body weight than the non-exercise group. This change was independent of any work performed.

Animals↗
PubMed1981

Modulation of Platelet thromboxane A2 and arterial prostacyclin by dietary vitamin E.

Platelets from vitamin E-deficient and vitamin E-supplemented rats generate the same amount of thromboxane A2 (TxA2) when they are incubated with unesterified arachidonic acid. Platelets from vitamin E-deficient rats produced more TxA2 than platelets from vitamin E-supplemented rats when the platelets are challenged with collagen. Arterial tissue from vitamin E-deficient rats generates less prostacyclin (PGI2) than arterial tissue from vitamin E- supplemented rats. The vitamin E effect with arterial tissue is observed when the tissue is incubated with and without added unesterified arachidonic acid. These data show that arterial prostacyclin synthesis is diminished in vitamin E-deficient rats. Vitamin E, in vivo, inhibits platelet aggregation both by lowering platelet TxA2 and by raising arterial PGI2.

Adenosine Diphosphate↗
PubMed1981

Age-related increase in prostacyclin production in the rat aorta.

Normal Sprague-Dawley rats convert a substantial percentage of exogenous arachidonic acid to prostacyclin. This conversion can be quantitated by an aqueous sampling technique utilizing thin layer chromatography and liquid scintillation counting. There is a clear age-related increase in this conversion that can be demonstrated in aortas from rats of 3 weeks to 20 weeks of age.

Aging↗
PubMed1981

Respiration-associated components of Mollicutes.

No cytochrome pigments were detected by difference (reduced minus oxidized) spectroscopy at liquid nitrogen temperature in whole-cell preparations or membrane fractions of Acholeplasma axanthum S273, Acholeplasma equifetale N93, Acholeplasma granularum BTS39, Acholeplasma laidlawii B-PG9, Acholeplasma modicum PG-49, Acholeplasma oculi 19L, Mycoplasma arginini G230, Mycoplasma arthritidis 07, Mycoplasma pneumoniae FH, and Mycoplasma pulmonis JB. All ten Mollicutes species examined contained iron of unknown function (3.0 to 15.3 nmol of iron per mg of protein). Relatively small amounts of acid-labile sulfide were found in all fractions (0.10 to 1.07 nmol of acid-labile sulfide per mg of protein). The data suggest that, as Mollicutes lack cytochrome pigments, they would synthesize most if not all adenosine triphosphate at the substrate level.

Cell Membrane↗
PubMed1977

Independent preclerkship study: a five year experience.

An independent study program (ISP) was instituted in 1970 for a group of 32 preclerkship medical students picked randomly from a group of 64 volunteers. The academic achievements of these classes, as measured by mean National Board scores, is compared with their classmates in the lecture discussion (LD) program where possible. The significant differences noted obtain even when the ISP students are compared only with LD students matched for premedical point-hour ratios and Medical College Admissions Test scores. These data attest to the overall success of the ISP program. The differences appear to us to be due mainly to factors related to motivation and maturity. The ease of preparations, convenience, and economy of the associated computer-assisted instruction make these methods attractive for use in residency training and continuing medical education where maturity and motivation may well be presumed.

Curriculum↗