Nitric oxide protects against cellular damage and cytotoxicity from reactive oxygen species.

Nitric oxide, NO, which is generated by various components of the immune system, has been presumed to be cytotoxic. However, NO has been proposed to be protective against cellular damage resulting during ischemia reperfusion. Along with NO there is often concomitant formation of superoxide/hydrogen peroxide, and hence a synergistic relationship between the cytotoxic effects of nitric oxide and these active oxygen species is frequently assumed. To study more carefully the potential synergy between NO and active oxygen species in mammalian cell cytotoxicity, we utilized either hypoxanthine/xanthine cell cytotoxicity, we utilized either hypoxanthine/xanthine oxidase (a system that generates superoxide/hydrogen peroxide) or hydrogen peroxide itself. NO generation was accomplished by the use of a class of compounds known as "NONOates," which release NO at ambient temperatures without the requirement of enzyme activation or biotransformation. When Chinese hamster lung fibroblasts (V79 cells) were exposed to hypoxanthine/xanthine oxidase for various times or increasing amounts of hydrogen peroxide, there was a dose-dependent decrease in survival of V79 cells as measured by clonogenic assays. However, in the presence of NO released from (C2H5)2N[N(O)NO]-Na+ (DEA/NO), the cytotoxicity resulting from superoxide or hydrogen peroxide was markedly abrogated. Similarly, primary cultures of rat mesencephalic dopaminergic cells exposed either to hydrogen peroxide or to hypoxanthine/xanthine oxidase resulted in the degradation of the dopamine uptake and release mechanism. As was observed in the case of the V79 cells, the presence of NO essentially abrogated this peroxide-mediated cytotoxic effect on mesencephalic cells.     

An electromyographic method for the assessment of naloxone-induced abstinence in morphine-dependent rats

Summary The electromyographic (EMG) activities of suprahyoideal muscle were recorded to measure naloxone-precipitated abstinence signs in morphine-dependent rats anesthetized with urethane (1 g/kg). Rats were rendered dependent on morphine by implanting 2 morphine pellets (75 mg each) and abstinence signs were induced by intravenous injections of various doses of naloxone at different times after pellet implantation. Three precipitated abstinence signs, a) myoclonic twitch activity (MTA), b) mastication, and c) body shakes were observed on EMG recordings after the injection of naloxone. Of these symptoms, only the MTA induced by naloxone (10 g/kg) occurred 4 h after pellet implantation and its sensitivity to naloxone increased with prolonged pellet implantation. Both mastication and precipitated shakes could be induced at 24 h. However, higher doses of naloxone were required to produce the shakes than is required to induce mastication. There appears to be a positive correlation between the intensity of naloxone-induced MTA and the degree of physical dependence on morphine. Since the MTA and mastication can be induced by low doses of naloxone in morphine-dependent rats, we suggest that these two parameters may be used to detect morphine abstinence signs in this species.Deceased February 13, 1979     

Giant ameloblastoma of the upper jaw

Ameloblastoma is the most frequently seen epithelial Odontogenic tumour, relatively uncommon, comprising about 1% of tumours and cysts arising from the Jaws.     

Predicting low birth weight delivery using maternal nutritional and uterine parameters

At the Institute of Medical Sciences, Banaras Hindu University in Varanasi, India, health workers took anthropometric measurements and hemoglobin level of 196 pregnant women at gestation of 37-41 weeks and of their singleton newborns to detect a combination of maternal nutritional and uterine parameters which could be used to screen mothers at high risk of delivering a low birth weight (LBW) infant ( 2500 g). The maternal anthropometric measurements included pre- and post-delivery weight, height, head and midarm circumference, fundal height, and abdominal girth. Weight, height, head and midarm circumference, and hemoglobin were significantly correlated with birth weight. Pre-delivery weight was better correlated than post-delivery weight with birth weight (r value = 0.4966 vs. 0.3494). The correlation between pre-delivery weight and birth weight remained, even when hemoglobin and one of the uterine parameters were controlled simultaneously. Hemoglobin was an independent significant predictor of birth weight, when all other variables were controlled simultaneously. Both fundal height and abdominal girth were significantly associated with birth weight, when all other variables were controlled simultaneously. Fundal height had a greater difference in means of birth weight than did abdominal girth (960 vs. 871 g). If the fundal height was less than 25 cm, all infants had a LBW. If the fundal height was greater than 35 cm, only one infant had a LBW. The multiple regression equation using pre-delivery weight, hemoglobin, fundal height, and abdominal girth (all independent significant parameters) to estimate birth weight accounted for 70.5% variation. Researchers tested the equation on 118 consecutive full-term singleton newborns. The equation predicted LBW in 32 of the 36 actual LBW deliveries. The estimated birth weights in the 4 actual but missed cases were 2620, 2600, 2566, and 2826 g. This equation can be successfully used to screen pregnant women for LBW.     

Evaluation of facial fat distribution using magnetic resonance imaging

Magnetic resonance imaging (MRI) provides noninvasive images of facial and neck fat for a variety of conditions. It accurately maps the soft tissues pre- and postoperatively, enabling surgeons to precisely and objectively assess results of soft tissue facial contouring and fat transplantation. The risks of MRI are few. It has the potential to provide aesthetic surgeons with a more scientific means of comparing various techniques of fat contouring.     

Application of a macromolecular contrast agent for detection of alterations of tumor vessel permeability induced by radiation.

Permeability of tumor vasculature can be a major barrier to successful drug delivery, particularly for high molecular weight agents such as monoclonal antibodies and their diagnostic or therapeutic conjugates. In this study, changes in permeability of SCCVII tumor vessels after radiation treatment were evaluated by dynamic magnetic resonance imaging as a function of time after irradiation using a generation-8 polyamidoamine dendrimer (G8-Gd-D)-based magnetic resonance imaging contrast agent shown previously to be confined to tumor blood vessels. Tumor irradiation consisted of either single doses (2-15 Gy) or various daily fractionated doses (5 days). A single radiation dose of 15 Gy resulted in significant transient image enhancement of the tumor tissue with a maximum occurring between 7 and 24 hours after radiation treatment. No observable enhancement was recorded for fractionated radiation doses. Use of dynamic magnetic resonance imaging coupled with G8-Gd-D provides an exquisite methodology capable of defining the timing of enhanced permeability of macromolecules in tumors after irradiation. Such information might be applied to optimize the efficacy of subsequent or concurrent therapies including radiolabeled antibodies or other anticancer agents in combination with external beam therapies.     

Chrome induced nasal septal perforation-An occupational hazard

86 patients, working in a chemical factory dealing with Chrome manufacturing job, were referred by Health Inspectai to F S 1 S Hospital O PD 32 patients out of above were found to be having Nasal septal perforation and were recommended to Medical Board for consideration of compensation as cases of Occupational hazard     

PHYSICO-CHEMICAL CHARACTERIZATION OF SEED OIL AND NUTRIENT ASSESSMENT OF ADENANTHERA PAVONINA, L: AN UNDERUTILIZED TROPICAL LEGUME

Analysis showed the seeds of Adenanthera pavonina contained appreciable amounts of proteins (29.44g/100g), crude fat (17.99g/100g), and minerals, comparable to commonly consumed staples. Total sugar was low (8.2g/100g) while starch (41.95g/100g) constitutes the major carbohydrates. Low levels of antinutrients were reported and methionine and cystine were the most deficient amino acids. Linoleic and oleic acids make up 70.7 percent of the total fatty acids. Free fatty acid levels were relatively high but peroxide and saponification values of 29.6mEqkg^-1 and 164.1mgKOHg^-1respectively point to a resemblance to oils processed for food. It was concluded that A. pavonina seeds represent a potential source of oil and protein that could alleviate shortages.     

Cerebral autoregulation in pediatric traumatic brain injury.

OBJECTIVE: The aims of this study were to document the incidence of impaired cerebral autoregulation in children with traumatic brain injury using transcranial Doppler ultrasonography and to examine the relationship between autoregulatory capacity and outcome in children following traumatic brain injury. DESIGN: Prospective cohort study. SETTING: Harborview Medical Center (level I pediatric trauma center) in Washington state. PATIENTS: Thirty-six children <15 yrs old with traumatic brain injury: Glasgow Coma Scale score <9 (n = 12, group 1), Glasgow Coma Scale score 9-12 (n = 12, group 2), and Glasgow Coma Scale score 13-15 (n = 12, group 3). INTERVENTIONS: Cerebral autoregulation testing was conducted during extracranial surgery. Mean middle cerebral artery flow velocities were measured using transcranial Doppler as mean arterial pressure was increased to whichever variable was greater: 20% above baseline or a set value (80 mm Hg for <9 yrs and 90 mm Hg for 9-14 yrs). Autoregulatory capacity was quantified by the Autoregulatory Index. Autoregulatory Index <0.4 was considered impaired cerebral autoregulation. Discharge outcome using the Glasgow Outcome Scale score was considered good if the Glasgow Outcome Scale score was > or =4. MEASUREMENTS AND MAIN RESULTS: Twenty-four (67%) of 36 children had an Autoregulatory Index > or =0.4. The incidence of impaired cerebral autoregulation was 42% (five of 12) in group 1, 42% (five of 12) in group 2, and 17% (two of 12) in group 3. Ten (42%) of the 24 children with intact cerebral autoregulation had a good outcome compared with only one of 12 (8%) children with impaired cerebral autoregulation (p =.04). Six of 12 (50%) children with impaired cerebral autoregulation had hyperemia compared with one of 24 (4%) children with intact cerebral autoregulation (p <.01). Hyperemia was associated with poor outcome (p =.01). CONCLUSIONS: The incidence of impaired cerebral autoregulation was greatest following moderate to severe traumatic brain injury. Impaired cerebral autoregulation was associated with poor outcome. Hyperemia was associated with impaired cerebral autoregulation and poor outcome.     

Neuroprotective strategies in parkinson’s disease: protection against progressive nigral damage induced by free radicals

Brain undergoes neurodegeneration when excess free radicals overwhelm antioxidative defense systems during senescence, head trauma and/or neurotoxic insults. A site-specific accumulation of ferrous citrate-iron complexes in the substantia nigra dopaminergic neurons could lead to exaggerated dopamine turnover, dopamine auto-oxidation, free radical generation, and oxidant stress. Eventually, this iron-catalyzed dopamine auto-oxidation results in the accumulation of neuromelanin, a progressive loss of nigral neurons, and the development of Parkinson's disease when brain dopamine depletion is greater than 80%. Emerging evidence indicates that free radicals such as hydroxyl radicals ((.-)OH) and nitric oxide ((.-)NO) may play opposite role in cell and animal models of parkinsonism. (.-)OH is a cytotoxic oxidant whereas oNO is an atypical neuroprotective antioxidant. (.-)NO and S-nitrosoglutathione (GSNO) protect nigral neurons against oxidative stress caused by 1-methyl-4-phenylpyridinium (MPP(+)), dopamine, ferrous citrate, hemoglobin, sodium nitroprusside and peroxynitrite. MPP(+), the toxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), increases the nigral uptake of iron complexes and dopamine overflow leading to the generation of (.-)OH, protein oxidation, lipid peroxidation, and associated retrograde degeneration. In addition to GSNO, MPP(+)-induced oxidative neurotoxicity can be prevented by antioxidants including selegiline, 7-nitroindazole, 17beta-estradiol, melatonin, alpha-phenyl-tert-butylnitrone and U78517F. Similar to selegiline, 7-nitroindazole is a MAO-B inhibitor, which blocks the bio-activation of MPTP and oxidative stress. Freshly prepared but not light exposed, (.-)NO-exhausted GSNO is about 100 times more potent than the classic antioxidant glutathione. Via S-nitrosylation, GSNO also inhibits proteolysis and cytotoxicity caused by caspases and HIV-1 protease. Furthermore, in addition to protection against serum deprivation stress, the induction of neuronal NOS1 in human cells increases tolerance to MPP(+)-induced neuro-toxicity since newly synthesized (.-)NO prevents apoptosis possibly through up-regulation of bcl-2 and down regulation of p66(shc). In conclusion, reactive oxygen species are unavoidable by-products of iron-catalyzed dopamine auto-oxidation, which can initiate lipid peroxidation, protein oxidation, DNA damage, and nigral loss, all of which can be prevented by endogenous and exogenous (.-)NO. Natural and man-made antioxidants can be employed as part of preventative or neuroprotective treatments in Parkinson's disease and perhaps dementia complexes as well. For achieving neuroprotection and neuro-rescue in early clinical parkinsonian stages, a cocktail therapy of multiple neuroprotective agents may be more effective than the current treatment with extremely high doses of a single antioxidative agent.