Leukocyte and platelet rich fibrin in the management of medication-related osteonecrosis of the jaw: A systematic review and meta-analysis.

BACKGROUND: Osteonecrosis of the jaw (ONJ) has a frequent adverse effect after the administration of nitrogenous bisphosphonates, as non-nitrogenous bisphosphonates are metabolized more rapidly and would produce this effect to a lesser extent. The objective of this study is to analyze the results obtained in the literature with the use of L-PRF in the treatment of ONJ through a systematic review and meta-analysis. MATERIAL AND METHODS: Medline (via PubMed), Cochrane, Web of Science and Grey Literature Database was screened from which 10 were selected. RESULTS: In the meta-analysis with full resolution, combining the use of L-PRF in the treatment of ONJ, a weighted proportion (PP) of 94.3% of complete resolution is obtained (95% CI: 91.2-97.4, p<0.001), with a low degree of heterogeneity, statistically significant (I2 = 29.02%; p<0.001). When analyzing the non-resolution data, a weighted proportion (PP) of 7.7% (95% CI: 3.6-11.9; p<0.001) was obtained with moderate heterogeneity (I2: 41.87%; p=0.112). In the meta-regression, no significant correlation was found between complete resolution and year of publication (intercept = 2.88, p=0.829). In consistency analysis no major changes in PP are identified when any of the studies are eliminated, demonstrating a high reliability in the combined results. CONCLUSION: L-PRF alone or in combination with other therapies in treatment of ONJ achieved high percentages of complete lesion resolution (94.3%). In studies where L-PRF is combined with other therapies, and where the effectiveness of the other therapy alone is analyzed, L-PRF has been shown higher percentages of resolution.

Una inusual causa de estrechez de la vía aérea laringotraqueal / An unusual cause of laryngotracheal airway narrowing

La enfermedad relacionada con inmunoglobulina (Ig) G4 es una enfermedad de reciente conocimiento que puede comprometer cualquier órgano teniendo preferencias por ciertas regiones del cuerpo, donde la región de cabeza y cuello es uno de sus principales puntos afectados, pudiendo comprometer tanto la órbita, glándulas salivales, glándulas lagrimales, glándula tiroides, cavidades paranasales, hueso temporal, faringe y laringe. Este último órgano es infrecuentemente comprometido, solo existiendo 12 casos registrados en la literatura antes de la publicación de este escrito. Presentamos un caso de una mujer de 49 años con historia de disnea frente a esfuerzo, diagnosticándose una estenosis subglótica la cual fue manejada quirúrgicamente con una reconstrucción laringotraqueal. En el estudio histopatológico se evidenció histología compatible con enfermedad relacionada con IgG4, por lo que se inició tratamiento médico con corticotera- pia oral por un lapso de 2 meses en conjunto con inmunología. Paciente luego de 4 años de seguimiento, no ha presentado recaídas, manteniendo un lumen subglótico adecuado.

Immunoglobulin (Ig) G4-related disease is a medical condition of recent knowledge that can compromise any organ, having preferences for certain regions of the body, where the head and neck region is one of the main affected points, being able to affect orbit, salivary glands, lacrimal glands, thyroid gland, paranasal cavities, temporal bone, pharynx and larynx. The latter is infrequently compromised, with only 12 cases registered in the literature before the publication of this writing. We present a case of a 49-year-old woman with a history of exertional dyspnea, diagnosed with a sub- glottic stenosis which was managed surgically with laryngotracheal reconstruction. The histopathological study revealed histology compatible with IgG4-related disease, so medical treatment with oral corticosteroid therapy was started for a period of 2 months in conjunction with immunology. After 4 years of follow-up, the patient has not presented relapses, maintaining an adequate subglottic lumen.

Clozapine produces potent antidopaminergic effects anatomically specific to the mesolimbic system.

Although weak as an antagonist at brain dopamine receptors, clozapine is very strongly antidopaminergic when measured by in vivo single-neuron electrophysiologic recording, in vivo brain microdialysis, in vivo brain voltammetric electrochemistry, in vivo electrical brain stimulation, or in vivo neurobehavioral techniques. Three aspects of clozapine's strong antidopaminergic actions are remarkable. First, clozapine's antidopaminergic potency is stronger than can be explained by its comparatively weak interaction with dopamine receptors, implying that a significant portion of its antidopaminergic action may be transsynaptic and secondary to actions on nondopamine neurotransmitter systems. Second, clozapine's strong antidopaminergic action is seen more reliably with chronic rather than acute administration, implying that some cumulative neurochemical process underlies the gradual recruitment of dopamine blockade. Third, and most remarkably, clozapine's strong antidopaminergic action is anatomically specific--present in the mesolimbic dopamine system but absent in the nigrostriatal dopamine system. This mesolimbic-specific dopamine blockade may underlie at least a portion of clozapine's atypical clinical profile.

Clozapine's functional mesolimbic selectivity is not duplicated by the addition of anticholinergic action to haloperidol: a brain stimulation study in the rat.

This study examined whether the anticholinergic potency of the clinically superior antipsychotic drug clozapine contributes to clozapine's anatomically-selective functional inhibition of the mesolimbic dopamine (DA) system, using an electrical brain-stimulation reward (BSR) paradigm in rats that has been previously shown to be highly sensitive to clozapine's mesolimbic functional selectivity. Rats were chronically administered saline, clozapine, haloperidol, or haloperidol plus the anticholinergic compound trihexyphenidyl, and threshold sensitivity of the mesolimbic and nigrostriatal DA systems was assessed using the BSR paradigm, to infer degree of functional DA blockade produced by the chronic drug regimens. Chronic saline produced no change in either DA system. Congruent with previous findings, chronic clozapine powerfully inhibited the mesolimbic DA system but spared the nigrostriatal DA system. Also congruent with previous findings, chronic haloperidol powerfully inhibited both DA systems. Compared to chronic haloperidol alone, chronic haloperidol plus chronic trihexyphenidyl exerted diminished anti-DA action in both the mesolimbic and nigrostriatal DA systems. These results suggest that clozapine's anticholinergic potency is not an adequate explanation for its functional mesolimbic selectivity.

Delta 9-tetrahydrocannabinol produces naloxone-blockable enhancement of presynaptic basal dopamine efflux in nucleus accumbens of conscious, freely-moving rats as measured by intracerebral microdialysis.

This study examined the effects of acute administration of delta-9-tetrahydrocannabinol (delta 9-THC), the psychoactive ingredient in marijuana, on extracellular efflux of dopamine (DA) and its metabolites as measured by in vivo microdialysis in nucleus accumbens of conscious, freely-moving rats. delta 9-THC, at low doses (0.5-1.0 mg/kg), which significantly enhance brain stimulation reward (intracranial self-stimulation), significantly increased DA efflux in nucleus accumbens. Augmentation of DA efflux by delta 9-THC was abolished by removal of calcium (Ca++) ions from the perfusion fluid, indicating a Ca(++)-dependence of delta 9-THC's action. Augmentation of DA efflux by delta 9-THC was either totally blocked or significantly attenuated by doses of naloxone as low as 0.1 mg/kg. Given the postulated role of mesocorticolimbic DA circuits in mediating and/or modulating brain stimulation reward, the present data raise the possibility that marijuana's rewarding effects, and hence its euphorigenic effects and abuse potential, may be related to pharmacological augmentation of presynaptic DA mechanisms. Additionally, the DA mechanisms enhanced by marijuana appear to be modulated by an endogenous opioid peptide system.

Facilitation of brain stimulation reward by delta 9-tetrahydrocannabinol.

The present experiment explored whether delta 9-tetrahydrocannabinol (delta 9-THC), the psychoactive ingredient in marijuana, shares with other drugs of abuse the ability to facilitate brain stimulation reward acutely, as measured by electrical intracranial self-stimulation (ICSS). Laboratory rats were implanted with stimulation electrodes in the medial forebrain bundle, and trained to stable performance on a self-titrating threshold ICSS paradigm. delta 9-THC, at a dose believed pharmacologically relevant to moderate human use of marijuana, acutely lowered ICSS thresholds, suggesting that marijuana acts on similar CNS hedonic systems to most other drugs of abuse.

Overview of chemical sampling techniques.

Although many of the ideas for sampling the chemical microenvironment of the brain were present, at least in nascent form, three decades ago or more, the last 10 years have witnessed a particularly spectacular surge of development, refinement, and use. We are now able to measure virtually any endogenous brain chemical in vivo at commendable levels of sensitivity, selectivity, and speed. The long-dreamt-of goal of being able to correlate neurochemical events with ongoing behavior and/or presentation of salient environmental cues and stimuli has already been largely achieved. Further refinements of existing techniques may well lead to levels of analysis inconceivable even a few years ago. The implications for theory-building and hypothesis-testing are enormous, particularly within such essentially virgin domains as behavioral neuroscience and biological psychiatry. These are truly exciting times.

Analgesic effects of intraventricular and intrathecal injection of morphine and ketocyclazocine in the infant rat.

Little is known of the neural bases of analgesia in immature animals. This experiment examined the effects of intracerebroventricular (i.c.v.) and intrathecal (i.t.) administration of morphine or ketocyclazocine in tests of antinociception in rats aged 3 to 14 days of age. Analgesia tests were conducted using both thermal and mechanical (pressure) noxious stimuli applied to the forepaw, hindpaw or tail. In the 3-day-old morphine-injected i.c.v. produced analgesia in the forepaws when either the mechanical or thermal noxious stimulus was used. There was no effect when the hindpaw or tail was tested. At 10 days of age, when the mechanical stimulus was used, morphine was analgesic in tests on all three appendages but was only effective in the forepaw when the thermal stimulus was used. Morphine was fully effective in all tests with both stimuli at 14 days of age. Ketocyclazocine had no consistent effect when given i.c.v. When injected i.t., morphine produced analgesia in the forepaws in the thermal test at 4 days of age and in all appendages by 10 days. When the mechanical test was used, morphine was effective in all appendages at all ages tested. Ketocyclazocine was analgesic at all appendages for the mechanical stimulus at all ages but was only transiently effective in the thermal test. The results demonstrate differential development of analgesia mediated at different levels of the neural axis and are consistent with the development of descending inhibitory that may mediate analgesia induced by i.c.v. injections of morphine. Neural mechanisms that are involved in the analgesic effects of these drugs against the two types of stimuli are also developmentally distinct.

Serotonin denervation enhances responsiveness of presynaptic dopamine efflux to acute clozapine in nucleus accumbens but not in caudate-putamen.

Clozapine alters mesolimbic dopamine (DA) function but spares nigrostriatal DA function in laboratory animals, but the underlying mechanism is unknown. In the present study, acute intraperitoneal injection of clozapine (5-40 mg/kg) increased extracellular DA levels in nucleus accumbens (Acb) and caudate-putamen (CPu) of awake, freely moving rats as measured by in vivo brain microdialysis, without anatomic selectivity. However, in serotonin (5HT)-denervated rats acute clozapine preferentially enhanced DA levels in Acb as compared to CPu. Since (i) up-regulation of 5HT receptors on DA neurons may result from 5HT denervation, (ii) clozapine has potent anti-5HT action, and (iii) 5HT receptors are more dense in Acb than CPu, these data appear to add additional weight to previous suggestions that a serotonergic mechanism may partly underlie clozapine's mesolimbic selectivity.

Effects of acute and chronic clozapine on dopaminergic function in medial prefrontal cortex of awake, freely moving rats.

We previously showed that chronic administration of the clinically atypical and clinically superior antipsychotic drug clozapine selectively reduces dopamine (DA) release in the nucleus accumbens but not neostriatum, and that this effect appears mediated by anatomically selective mesolimbic DA depolarization blockade. The present study extends that research to another mesocorticolimbic DA locus, the medial prefrontal cortex. Acute clozapine challenge (5-40 mg/kg i.p.) produced dose-dependent increased extracellular levels of DA and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the medial prefrontal cortex of awake, free-moving rats as measured by in vivo brain microdialysis. Chronic clozapine treatment (20 mg/kg/day for 21 days) did not significantly change basal extracellular levels of DA, DOPAC or HVA. Acute clozapine challenge on day 22 in the chronic clozapine-treated animals produced no significant differences in medial prefrontal cortex DA, DOPAC or HVA as compared to chronic vehicle-treated animals, indicating that tolerance to clozapine does not develop in the mesocortical DA system, in contrast to the mesolimbic system. The DA agonist apomorphine (100 micrograms/kg) produced decreased basal extracellular levels of DA, DOPAC and HVA in medial prefrontal cortex of both chronic clozapine-treated and chronic vehicle-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Morphine-induced downregulation of mu-opioid receptors in neonatal rat brain.

Chronic administration of morphine to pre- and postnatal rats produced a marked decrease in brain mu-opioid receptor density with-out change in receptor affinity. No significant changes in delta- or kappa-receptors were observed. This downregulation was accompanied by tolerance to the analgesic actions of morphine. In neonates exposed to morphine from postnatal day one, mu-receptor number was significantly depressed until postnatal day 8, then increased gradually to control levels by day 14 of treatment. Longer treatment produced no further change in opioid receptors. These data represent the first demonstration of in vivo downregulation of brain mu-opioid receptors following morphine administration and provide evidence for a unique plasticity of the immature opioid receptor system.

Kappa opioid receptor-mediated analgesia in the developing rat.

The prototypic kappa opiate ketocyclazocine produced robust analgesia in 10-day-old rats in the tail-flick nociceptive test. The kappa-opiate behavioral response coincided with the onset of a rapid rise to adult levels in brain kappa receptor site density. In contrast, morphine (prototypic mu opiate) was without marked effect until 14 days of age. The period of rapid mu receptor increase did not take place until days 14-16, which was after kappa receptor levels had already plateaued. Further, there was no or incomplete cross-tolerance between ketocyclazocine and morphine at 14 days of age. The present study, therefore, establishes a role for the kappa binding site in thermal analgesia in the tail flick test and differentiates its ontogenetic pattern from that of the mu receptor.

Ventral tegmental microinjection of delta 9-tetrahydrocannabinol enhances ventral tegmental somatodendritic dopamine levels but not forebrain dopamine levels: evidence for local neural action by marijuana's psychoactive ingredient.

Basal extracellular levels of dopamine (DA) and its metabolites in both ventral tegmental area (VTA) and nucleus accumbens (Acb) were simultaneously monitored by in vivo brain microdialysis in laboratory rats. Microinjection of 12 micrograms or 24 micrograms delta 9-tetrahydrocannabinol (delta 9-THC), the psychoactive ingredient in marijuana and hashish, into the VTA produced a dose-dependent increase in somatodendritic DA levels in VTA but failed to produce any simultaneous change in extracellular DA in Acb. Direct delta 9-THC perfusion (5 x 10(-5) and 2 x 10(-4) M) into Acb via the microdialysis probes caused a significant increase in extracellular DA levels in Acb. These findings suggest that (1) delta 9-THC has a facilitating effect on somatodendritic DA efflux, and (2) the elevation of Acb DA levels seen in our previous studies with systemic administration of delta 9-THC may result from local actions of delta 9-THC at or near the DA terminal projections in Acb.

Delta 9-tetrahydrocannabinol enhances presynaptic dopamine efflux in medial prefrontal cortex.

Acute administration of 1.0-2.0 mg/kg delta 9-tetrahydrocannabinol (delta 9-THC) increased presynaptic dopamine (DA) efflux in the medial prefrontal cortex of rats, as measured by intracerebral microdialysis in awake, behaving rats. These data are congruent with suggestions that (1) marijuana's euphorigenic effects and abuse potential may be related to augmentation of presynaptic DA mechanisms, and (2) the medial prefrontal cortex may be an important site of action for drugs of abuse in general and for delta 9-THC in particular.

Chronic treatment with clozapine selectively decreases basal dopamine release in nucleus accumbens but not in caudate-putamen as measured by in vivo brain microdialysis: further evidence for depolarization block.

As measured using in vivo brain microdialysis in conscious freely-moving rats, chronic treatment (20 mg/kg/day i.p. for 21 days) with the clinically atypical neuroleptic clozapine selectively reduced basal dopamine (DA) release in the nucleus accumbens (Acb) but not in caudate-putamen (CPu). Apomorphine (100 micrograms/kg s.c.) enhanced presynaptic Acb DA release in clozapine-treated rats, but reduced Acb DA release in vehicle-treated rats. These findings provide further evidence that depolarization block of mesolimbic DA neurons projecting to Acb but not of nigrostriatal DA neurons projecting to CPu may underlie clozapine's unusual clinical efficacy and its lack of production of extrapyramidal motoric effects.

Strain-specific facilitation of dopamine efflux by delta 9-tetrahydrocannabinol in the nucleus accumbens of rat: an in vivo microdialysis study.

This study tests the hypothesis that delta 9-tetrahydrocannabinol (delta 9-THC) has a strain-specific facilitatory effect on dopamine (DA) efflux in rat nucleus accumbens, a crucial forebrain convergence of reward-relevant DA neural fibers that has been implicated as a focal brain locus mediating the euphorigenic properties of drugs of abuse. The dependent variable is presynaptic DA efflux measured by in vivo microdialysis in the nucleus accumbens. The independent variables are: (1) intraperitoneal injections of delta 9-THC at 0.0 (vehicle), 0.5 and 1.0 mg/kg; (2) Sprague-Dawley vs Lewis strain rat. Results show that delta 9-THC produces a dose-dependent, strain-specific enhancement of basal DA efflux in Lewis strain rats. These results suggest that genetic variation influences drug abuse vulnerability.

Bartonellosis in Zamora Chinchipe province in Ecuador.

Human bartonellosis was investigated in the Ecuadorian province of Zamora Chinchipe; 17 cases were identified retrospectively from hospital records over the period 1984-1995, mostly from 6 communities in the provincial district of Zumba. A questionnaire concerning risk factors for disease transmission was administered in these 6 communities. Blood samples were taken from individuals with current febrile illnesses or skin lesions suggestive of bartonellosis. Samples for detection of Bartonella bacilliformis were also taken from all school-age children in communities where historical cases had been identified by questionnaire. No bacteriologically positive case was identified and no evidence of asymptomatic infection was detected. Risk factors for disease transmission, identified by the questionnaire, included the presence of sick or dying chickens and guinea-pigs. It was suggested that bartonellosis is a zoonosis with wild animals, probably rodents, as the reservoir. The widespread use of residual insecticides and the easy availability of antibiotics is likely to have modified the epidemiology of this disease over the last decade.

Treatment of human pulmonary paragonimiasis with triclabendazole: clinical tolerance and drug efficacy.

An open clinical trial to determine the efficacy and tolerability of postprandial doses of triclabendazole against Paragonimus mexicanus in 62 patients with pulmonary paragonimiasis from the Ecuadorian Amazon region was performed. Praziquantel was used as therapeutic control. Patients were allocated at random to the following 4 therapeutic regimens: triclabendazole, 5 mg/kg once daily for 3 d (16 patients), 10 mg/kg twice on one day (15 patients), and 10 mg/kg in a single dose (16 patients), and praziquantel, 25 mg/kg thrice daily for 3 d (15 patients). Clinical tolerance, based on the frequency and severity of adverse reactions, was superior in all 3 triclabendazole regimens to that of praziquantel. No alteration was observed in hepato-renal functions or haematological values. The clinical symptoms resolved at a comparable rate in all 4 treatment groups. A more rapid parasitological response to treatment, as determined by the reduction in the average number of parasite eggs found in sputum, was seen in patients treated with triclabendazole than with praziquantel. By day 90, 60 patients had no egg detected in their sputum; 2 patients, treated with a single dose of 10 mg/kg, had a few and were re-treated with triclabendazole (5 mg daily for 3 d). On day 365, none of the patients had eggs in their sputum. Triclabendazole can be recommended as an alternative drug of choice for the treatment of pulmonary paragonimiasis; it is as effective as praziquantel in clearing infections and better tolerated.

Trypanosoma cruzi isoenzyme variability in Ecuador: first observation of zymodeme III genotypes in chronic chagasic patients.

We have analysed by multilocus enzyme electrophoresis (MLEE) at 21 genetic loci 10 Trypanosoma cruzi stocks isolated from chronic chagasic patients and 3 stocks isolated from Triatoma dimidiata collected in human habitats from the coastal part of Ecuador (all stocks isolated in August-December 1998). Isoenzyme profiles were compared to those of 4 laboratory-cloned stocks representing the major phylogenetic subdivisions of T. cruzi. This parasite's genetic variability in Ecuador proved to be considerable, even in this limited sample, since all main isoenzyme genotypes were recorded. Four stocks from patients were identical at all loci to the reference stock MNcl2 ('major clonet #39'; T. cruzi II) isolated in Chile. The 3 stocks isolated from T. dimidiata were closely related to the formerly described zymodeme I (T. cruzi I). Finally, 3 stocks from chronic chagasic patients (one with an asymptomatic form, 2 with a cardiac-digestive form) were closely related to the formerly described zymodeme III (presently not classified in either T. cruzi I or T. cruzi II). This is the first observation of this category of T. cruzi genotypes in chronic chagasic patients. In the past it was recorded only in acute patients, wild mammals and wild triatomine bugs. The epidemiological implications of these results are discussed.

Place conditioning with morphine and phencyclidine: dose dependent effects.

In a place conditioning paradigm, rats were exposed to one of two distinctive environments following injection of drug or vehicle. Preference was measured under drug free conditions by allowing subjects free access to both settings and measuring where they spent more time. Comparisons were made between morphine and saline; PCP and saline; and one of several doses of morphine and a standard dose. Morphine was preferred over saline and, when compared to the reference dose, lower doses of morphine were less preferred and higher doses more preferred. PCP was never preferred over saline and under some conditions produced a conditioned place aversion. The ability to generate dose dependent effects with morphine should allow more sophisticated studies in which shifts in dose response curves are required.