Biomedical subjects

M H Biros

Publications and source records attributed to M H Biros.

8 recordsLinked to original sources

PubMed1991

Experimental head trauma models: a clinical perspective.

The investigation of the biomechanics, biochemistry and functional changes occurring with significant head trauma is a very active and interesting area of scientific research by investigators of many disciplines. Using a variety of head trauma model systems, a tremendous amount of basic knowledge on what occurs to the injured brain has been accumulated over the last two to three decades. Ongoing research on the basic pathophysiology of head trauma as well as on the investigation of potentially useful therapeutic modalities is a current research trend. While a cross-disciplinary approach is necessary and useful in this rapidly expanding area of investigation, much of what is reported is technically difficult to understand and the clinical implications of the stated findings may not be clearly obvious. Some model systems are more suitable to study particular traumatic lesions that are others, and some systems have built-in limitations which must be acknowledged in data interpretation. This articles describes and evaluates some of the currently used head trauma model systems and reviews these systems from a clinician's standpoint.

Animals↗

PubMed1988

Comparison of sodium bicarbonate with dichloroacetate treatment of hyperlactatemia and lactic acidosis in the ischemic rat.

Serum lactic acidosis is characterized by a pH less than 7.25 and lactate greater than 5 mEq. Although sodium bicarbonate (NaHCO3) is standard treatment for this condition, clinical and experimental studies suggest that high doses of NaHCO3 may be ineffectual or even detrimental to brain, cardiovascular, and respiratory function, as well as survival. For this reason, low dose therapy with NaHCO3 has been recommended. Sodium dichloroacetate (NaDCA) has been used successfully to treat clinical and experimentally-induced lactic acidosis. The present study was designed to compare the effects of low dose NaHCO3 with NaDCA on blood pressure, blood chemistries and brain metabolites in rats with a low flow-induced (Type A, the most common type) lactic acidosis. Fasted male Wistar rats were subjected to cerebral ischemia and systemic hypotension for 30 min at which time, if the pH or HCO-3 fell to 7.2 or 10, respectively, the rat was treated with NaHCO3, NaDCA, or an equal volume of sterile water. Over the 30 min of recirculation that followed ischemia, treatment had no effect on blood pressure or glucose or on brain glucose or glycogen. NaHCO3 had no effect on lactate but appeared to stabilize pH and increase HCO3- more than in sham- or NaDCA-treated rats. Although NaDCA caused a greater increase in HCO3- than sham treatment, pH continued to decline. However, lactate decreased more in NaDCA- than in sham- or NaHCO3- treated rats. These results suggest that low dose NaHCO3 is not detrimental in this model; however, although NaHCO3 stabilized pH, it did not rapidly correct the acidosis. NaDCA at this dose had no effect on the acidosis but was effective in decreasing lactate. Since serum lactate has previously correlated with survival and since higher doses of NaDCA have corrected lactic acidosis in other studies, future evaluation of postischemic treatment with higher doses of NaDCA is warranted.

Acetates↗

PubMed1987

Mechanisms of ischemic cerebral injury.

Normal compensatory mechanisms protect the central nervous system (CNS) from moderate hypoxia and ischemia; however, after more severe ischemia progressive brain hypoperfusion ensues and irreversible damage occurs. Ischemic brain injury remains greatly significant clinically and elucidating the determinants of ischemic neuronal injury and death continues to challenge researchers. Although altered perfusion and decreased energy charge may contribute to the production of irreversible damage, the distribution of lesions seen after insult does not correspond with the degree of ischemic blood flow impairment, nor can neuronal energy deprivation explain the cell damage. Other factors, such as derangements in astrocyte function, calcium homeostasis, free radical metabolism, acid-base regulation and excitatory neurotransmitters also probably mediate ischemic neuronal death. Continued investigation to establish the cellular pathophysiology of cerebral ischemia can guide rational research and therapeutic strategies.

Acid-Base Equilibrium↗

PubMed1987

Brain lactate during partial global ischemia and reperfusion: effect of pretreatment with dichloroacetate in a rat model.

Elevated cerebral lactate levels following cerebral ischemia have been associated with brain cell damage and death. We previously found that pre- or postischemia treatment with dichloroacetate (DCA), presumably by its activation of brain pyruvate dehydrogenase, effectively lowers cerebral lactate levels in rats subjected to 30 minutes of partial global ischemia (PGI) followed by 30 minutes of recirculation. The goal of the present study was to determine the effects of preischemia DCA treatment on cortical lactate levels during the ischemia period or during early recirculation. Rats (four in each group) received preischemia treatment with DCA and were then subjected to 0, 10, or 30 minutes of PGI or 30 minutes of PGI followed by 15 minutes of recirculation. Cortical lactate levels in pretreated animals were not significantly different from lactate levels of untreated rats at any time during PGI, but were significantly lower than levels in untreated rats at 15 minutes of recirculation (P less than .05, ANOVA). These results suggest that preischemia treatment with DCA does not limit the accumulation of cortical lactate during PGI but may promote its clearance during recirculation following PGI. If reperfusion events influence the degree of brain cell injury, DCA may enhance cell recovery by lower cortical lactate levels in the reperfusion period.

Acetates↗

PubMed1987

Dichloroacetate treatment of ischemic cerebral lactic acidosis in the fed rat.

Despite advances in cardiac resuscitation, ischemic brain injury remains generally untreatable. Animal studies of brain ischemia associate brain lactate levels of more than 18 mumol/g with irreversible neuronal injury. Lowering brain lactate therefore may prevent or minimize ischemic brain necrosis. Earlier studies in our laboratory using fasted rats demonstrated that sodium dichloroacetate (DCA) decreases ischemic brain lactate when given either before or immediately after partial global ischemia (PGI). Other investigators have shown that fed animals have more glucose and generate higher lactate levels by anaerobic metabolism during PGI. We evaluated the ability of DCA to lower brain lactate in fed male Wistar rats subjected to PGI. Four groups (n = 6 each) were studied--PGI and control rats with either placebo or DCA treatment. PGI was induced for 30 minutes by combining bilateral carotid artery occlusion with hemorrhagic hypotension. This was followed by release of carotid occlusion, reinfusion of shed blood, and immediate treatment with either DCA (25 mg/kg, IV) or placebo. Thirty minutes later brains were frozen in situ with liquid nitrogen for extraction and measurement of tissue glucose, glycogen, and lactate. Blood glucose and serum lactate were monitored throughout the experiment. No significant differences were found between the two PGI groups in brain glucose, brain glycogen, or ischemia-induced elevations in blood glucose and serum lactate. However, brain lactate was significantly lower in DCA-treated (12.5 mumol/g) than in untreated (22.8 mumol/g) PGI rats (P less than .001). In addition, all untreated PGI rats had levels of more than 18 mumol/g, and therefore were at high risk for neuronal necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗

PubMed1986

Postinsult treatment of ischemia-induced cerebral lactic acidosis in the rat.

Cerebral ischemic insult is one of the most clinically significant conditions leading to irreversible brain cell damage and death. Animal studies have suggested that lowered intracellular pH due to the severe brain lactic acidosis following ischemia interferes with normal cell structure and function and leads to brain cell necrosis. Therefore, efforts directed to decreasing brain lactate may be beneficial in preventing brain cell damage and death. The goal of our study was to evaluate the effectiveness of postinsult treatment with dichloroacetate (DCA) in controlling increases in brain lactate following partial global ischemia (PGI) in rats. PGI was induced by bilateral carotid artery occlusion and induced hypotension. Animals that received DCA immediately after a 30-minute ischemic insult (n = 5) or 15 minutes after the end of an ischemic insult (n = 5) had cortical lactate levels that were significantly lower (P less than .005) than lactate levels in untreated insulted animals and that were not significantly different than those previously obtained with preinsult DCA treatment in rats subjected to 30 minutes of PGI. Treatment of rats with DCA following PGI may be effective in reducing cortical lactate levels and hence may limit irreversible damage to brain cells following cerebral ischemia.

Acetates↗

PubMed1979

Salivary and plasma IgA of seizure subjects receiving phenytoin.

Immunoglobulin A, phenytoin, and protein were determined in plasma, unstimulated and stimulated whole saliva and stimulated and unstimulated parotid saliva from seizure subjects, aged 18 or more, who had ingested phenytoin for 1 year or more from controls. Patient subgroups with low plasma IgA and with gingival overgrowth were evaluated separately. Plasma and salivary phenytoin and ratios of salivary to plasma phenytoin concentrations corresponded to published reports. Plasma IgA was significantly decreased in the total patient group. However, salivary IgA expressed as the concentration or as the proportion of salivary protein, with one exception, was not significantly decreased in any type of saliva from the total patient group or subgroups. Significant phenytoin induced increases in salivary IgA were noted. IgA secretion rate by the parotid gland was significantly increased in the total patient group. This investigation does not indicate a deficiency of oral IgA from chronic phenytoin ingestion. Thus, it appears unlikely that decreased oral IgA with a consequent enhanced susceptibility to inflammation contributes to phenytoin associated gingival overgrowth.

Adolescent↗

PubMed1978

Doubling time alpha-aminoisobutyrate transport and calcium exchange in cultured fibroblasts from cystic fibrosis and control subjects.

Population doubling time, kinetics of transport of alpha-aminoisobutyrate (AIB) and calcium (Ca) exchange were studied in skin fibroblast monolayers obtained from 5 subjects with cystic fibrosis (CF) and 5 age- and sex-matched controls. Population doubling time as estimated from cell count, protein and DNA was no different in the two groups. KM, Vmax, maximal uptake and time of half maximal uptake of AIB were no different in the two groups. Intracellular Ca pool size based on exchange of 45Ca with unlabelled Ca was significantly greater in monolayers from CF subjects.

Aminoisobutyric Acids↗