Effect of theobromine on dissolution of uric acid kidney stones.

PURPOSE: Uric acid renal lithiasis has a high prevalence and a high rate of recurrence. Removal of uric acid stones can be achieved by several surgical techniques (extracorporeal shock wave lithotripsy, endoscopy, laparoscopy, open surgery). These stones can also be eliminated by dissolution within the kidneys, because the solubility of uric acid is much greater when the pH is above 6. At present, N-acetylcysteine with a urinary basifying agent is the only treatment proposed to increase the dissolution of uric acid stones. In this paper, we compare the effect of theobromine and N-acetylcysteine on the in vitro dissolution of uric acid calculi in artificial urine at pH 6.5. METHODS: The dissolution of uric acid renal calculi was performed in a temperature-controlled (37 °C) chamber. A peristaltic pump was used to pass 750 mL of synthetic urine (pH 6.5) through a capsule every 24 h. Stone dissolution was evaluated by measuring the change in weight before and after each experiment. RESULTS: N-acetylcysteine increased the dissolution of uric acid calculi, but the effect was not statistically significant. Theobromine significantly increased the dissolution of uric acid calculi. Both substances together had the same effect as theobromine alone. The addition of theobromine to a basifying therapy that uses citrate and/or bicarbonate is a potential new strategy for the oral chemolysis of uric acid stones. CONCLUSION: Theobromine may prevent the formation of new stones and increase the dissolution of existing stones.

Neuroprotective Effects of Theobromine in permanent bilateral common carotid artery occlusion rat model of cerebral hypoperfusion.

Cerebral hypoperfusion (CH) is a common underlying mechanism of dementia disorders linked to aberrations in the neurovascular unit. Hemodynamic disturbances adversely affect cellular energy homeostasis that triggers a sequence of events leading to irrevocable damage to the brain and neurobehavioral discrepancies. Theobromine is a common ingredient of many natural foods consumed by a large population worldwide. Theobromine has shown health benefits in several studies, attributed to regulation of calcium homeostasis, phosphodiesterase, neurotransmission, and neurotrophins. The current study evaluated the neuroprotective potential of theobromine against CH in the permanent bilateral common carotid artery occlusion (BCCAO) prototype. Wistar rats were distributed in Sham-operated (S), S + T100, CH, CH + T50, and CH + T100 groups. Animals received permanent BCCAO or Sham treatment on day 1. Theobromine (50, 100 mg/kg) was given orally in animals subjected to BCCAO for 14 days daily. CH caused neurological deficits (12-point scale), motor dysfunction, and memory impairment in rats. Treatment with theobromine significantly attenuated neurological deficits and improved sensorimotor functions and memory in rats with CH. In biochemistry investigation of the entire brain, findings disclosed reduction in brain oxidative stress, inflammatory intermediaries (tumor necrosis factor-α, interleukin-1ß and - 6, nuclear factor-κB), markers of cell demise (lactate dehydrogenase, caspase-3), acetylcholinesterase activity, and improvement in γ-aminobutyric acid quantity in rats that were given theobromine for 14 days daily after CH. Histopathological analysis substantiated attenuation of neurodegenerative changes by theobromine. The findings of this study indicated that theobromine could improve neurological scores, sensorimotor abilities, and memory in CH prototype.

Sub-chronic and chronic toxicity evaluation of 7-methylxanthine: a new molecule for the treatment of myopia.

Myopia (nearsightedness) is a vision disorder with a blurring of far objects, affect millions worldwide. 7-methylxanthine (7-MX) is a molecule that is presently under clinical investigation for the treatment of myopia. In the present study, we have investigated sub-chronic and chronic toxicity of 7-MX in comparison to other clinically used methylxanthines i.e., caffeine and theobromine as per OECD guidelines 408 and 452. 7-MX was administered orally for 90 days at three different doses of 250, 500, and 1000 mg/kg for sub-chronic toxicity evaluation, and at a limit dose of 1000 mg/kg in 180 days chronic toxicity evaluation in rats. In sub-chronic treatment, 7-MX showed no mortality and signs for toxicity in any group, whereas 10% and 40% mortality with signs for toxicity were observed in caffeine and theobromine treated groups, respectively. A similar, safety profile was observed with 7-MX in 180 days of chronic toxicity study. Further, to confirm any morphological changes in organs; ultrasound and X-rays analysis were performed and no changes in the size of organs, cyst formation, fluid retention, or crystal formation was observed. Thus, the repeated dose study of 7-MX for 180 days may augment the possibility of using 7-MX clinically for the safe and effective treatment of myopia.

Inflammatory Microenvironment and Adipogenic Differentiation in Obesity: The Inhibitory Effect of Theobromine in a Model of Human Obesity In Vitro.

OBJECTIVE: Obesity is considered a clinic condition characterized by a state of chronic low-grade inflammation. The role of macrophages and adipocytokines in adipose tissue inflammation is in growing investigation. The physiopathological mechanisms involved in inflammatory state in obesity are not fully understood though the adipocytokines seem to characterize the biochemical link between obesity and inflammation. The aim of this work is to analyze the effect of theobromine, a methylxanthine present in the cocoa, on adipogenesis and on proinflammatory cytokines evaluated in a model of fat tissue inflammation in vitro. METHODS: In order to mimic in vitro this inflammatory condition, we investigated the interactions between human-like macrophages U937 and human adipocyte cell lines SGBS. The effect of theobromine on in vitro cell growth, cell cycle, adipogenesis, and cytokines release in the supernatants has been evaluated. RESULTS: Theobromine significantly inhibits the differentiation of preadipocytes in mature adipocytes and reduces the levels of proinflammatory cytokines as MCP-1 and IL-1ß in the supernatants obtained by the mature adipocytes and macrophages interaction. CONCLUSION: Theobromine reduces adipogenesis and proinflammatory cytokines; these data suggest its potential therapeutic effect for treating obesity by control of macrophages infiltration in adipose tissue and inflammation.

Effect of theobromine-containing toothpaste on dentin tubule occlusion in situ.

OBJECTIVES: Dentin hypersensitivity (DH) is treated by either occlusion of dentin tubules or nerve desensitization. This in situ study compared dentin tubules occlusion by theobromine-containing dentifrices with (Theodent-classic-F®, TCF) and without (Theodent-classic®, TC) fluoride with 1,500 ppm fluoride toothpaste, Colgate®-Regular (Fluoride) and Novamin®-containing toothpaste, Sensodyne®-5000-Nupro (Novamin®). METHODS: Each subject wore four intraoral appliances bearing dentin blocks while using one of four test dentifrices (n = 20/dentifrice) twice daily for 7 days. The four appliances were removed successively after 1, 2, 3, and 7 days. Treated blocks and their control (untreated) blocks were examined with scanning electron microscopy (SEM). Effects were compared statistically (ANOVA/Tukey's) based on percentage of surface area covered by deposited precipitate layer (%DPL) and percentage of fully open (%FOT), partially occluded (%POT), and completely occluded (%COT) tubules in each block calculated relative to the number of tubules in their control blocks. RESULTS: SEM observation indicated an increased %COT and %DPL over time. After 1 and 2 days, %COT was comparable with TC and TCF, and significantly (p < 0.05) higher compared with Novamin® and Fluoride. Following 3 and 7 days, %COT was comparable among TC, TCF, and Novamin®, but remained significantly lower in Fluoride. At any time, %DPL was significantly (p < 0.05) higher in TC, TCF, and Novamin® compared with Fluoride. CONCLUSIONS: Theobromine-containing toothpastes with and without fluoride have equal potential in occluding dentin tubules within a shorter time period than Novamin®-containing toothpaste; however, the three demonstrated equal potential after 1 week, but not the fluoride toothpaste. CLINICAL RELEVANCE: Theobromine-containing toothpaste promoted dentin tubule occlusion thus shows potential to relief DH.

The wonders of the Wanderer.

Vagus is Latin for wandering, and the vagus nerve fully deserves this name due to its extensive distribution through the body. Indeed, one of the lines of the song that accompanied the 2012 G. L. Brown Prize Lecture exaggerates this diversity, 'My function's almost anythin', and vagus is my name'. Alteration of vagal activity was first investigated in the 1880s as a treatment for epilepsy, and vagus nerve stimulation is now an approved treatment for refractory epilepsy and depression in the USA, despite an incomplete understanding of the mechanisms involved. Vagus nerve stimulation could be beneficial in many other conditions, including heart failure, tinnitus, chronic hiccups, Alzheimer's disease and inflammatory diseases. Inhibition of vagal activity could also be beneficial in some conditions, e.g. reducing activation of vagal respiratory afferents to treat chronic cough. This review discusses evidence underlying some current and potential therapeutic applications of vagal modulation, illustrating the wonders of the Wanderer.

Remineralization of artificial enamel lesions by theobromine.

OBJECTIVE: This study investigated the remineralization potential of theobromine in comparison to a standard NaF dentifrice. METHODS: Three tooth blocks were produced from each of 30 teeth. Caries-like lesion was created on each block using acidified gel. A smaller block was cut from each block for baseline scanning electron microscopy imaging and electron-dispersive spectroscopy (EDS) analysis for surface Ca level. A tooth slice was cut from each lesion-bearing block for transverse microradiography (TMR) quantification of baseline mineral loss (Δz) and lesion depth (LD). Then baseline surface microhardness (SMH) of each lesion was measured. The three blocks from each tooth were assigned to three remineralizing agents: (1) artificial saliva; (2) artificial saliva with theobromine (0.0011 mol/l), and (3) NaF toothpaste slurry (0.0789 mol/l F). Remineralization was conducted using a pH cycling model with storage in artificial saliva. After a 28-day cycle, samples were analyzed using EDS, TMR, and SMH. Intragroup comparison of pre- and posttest data was performed using t tests (p < 0.05). Intergroup comparisons were performed by post hoc multistep comparisons (Tukey). RESULTS: SMH indicated significant (p < 0.01) remineralization only with theobromine (38 ± 32%) and toothpaste (29 ± 16%). With TMR (Δz/lD), theobromine and toothpaste exhibited significantly (p < 0.01) higher mineral gain relative to artificial saliva. With SMH and TMR, remineralization produced by theobromine and toothpaste was not significantly different. With EDS, calcium deposition was significant in all groups, but not significantly different among the groups (theobromine 13 ± 8%, toothpaste 10 ± 5%, and artificial saliva 6 ± 8%). CONCLUSION: The present study demonstrated that theobromine in an apatite-forming medium can enhance the remineralization potential of the medium.

Guarana (Paullinia cupana) ameliorates memory impairment and modulates acetylcholinesterase activity in Poloxamer-407-induced hyperlipidemia in rat brain.

Hyperlipidemia is a risk factor for the development of cognitive dysfunction and atherosclerosis. Natural compounds have recently received special attention in relation to the treatment of disease due to their low cost and wide margin of safety. Thus, the aim of this study was to determine the possible preventive effect of guarana powder (Paullinia cupana) on memory impairment and acetylcholinesterase (AChE) activity in the brain structures of rats with Poloxamer-407-induced hyperlipidemia. Adult male Wistar rats were pretreated with guarana (12.5, 25 and 50mg/kg/day) and caffeine (0.2mg/kg/day) by gavage for a period of 30days. Simvastatin (0.04mg/kg) was administered as a comparative standard. Acute hyperlipidemia was induced with intraperitoneal injections of 500mg/kg of Poloxamer-407. Memory tests and evaluations of anxiety were performed. The cortex, cerebellum, hippocampus, hypothalamus and striatum were separated to assess acetylcholinesterase activity. Our results revealed that guarana powder was able to reduce the levels of TC and LDL-C in a manner similar to simvastatin. Guarana powder also partially reduced the liver damage caused by hyperlipidemia. Guarana was able to prevent changes in the activity of AChE and improve memory impairment due to hyperlipidemia. Guarana powder may therefore be a source of promising phytochemicals that can be used as adjuvant therapy in the management of hyperlipidemia and cognitive disorders.

Theobromine inhibits sensory nerve activation and cough.

Cough is a common and protective reflex, but persistent coughing is debilitating and impairs quality of life. Antitussive treatment using opioids is limited by unacceptable side effects, and there is a great need for more effective remedies. The present study demonstrates that theobromine, a methylxanthine derivative present in cocoa, effectively inhibits citric acid-induced cough in guinea-pigs in vivo. Furthermore, in a randomized, double-blind, placebo-controlled study in man, theobromine suppresses capsaicin-induced cough with no adverse effects. We also demonstrate that theobromine directly inhibits capsaicin-induced sensory nerve depolarization of guinea-pig and human vagus nerve suggestive of an inhibitory effect on afferent nerve activation. These data indicate the actions of theobromine appear to be peripherally mediated. We conclude theobromine is a novel and promising treatment, which may form the basis for a new class of antitussive drugs.

The potential of methylxanthine-based therapies in pediatric respiratory tract diseases.

Caffeine, theophylline and theobromine are the most known methylxanthines as they are present in coffee, tea and/or chocolate. In the last decades, a huge experimental effort has been devoted to get insight into the variety of actions that these compounds exert in humans. From such knowledge it is known that methylxanthines have a great potential in prevention, therapy and/or management of a variety of diseases. The benefits of methylxanthine-based therapies in the apnea of prematurity and their translational potential in pediatric affections of the respiratory tract are here presented.

The cardiovascular benefits of dark chocolate.

Dark chocolate contains many biologically active components, such as catechins, procyanidins and theobromine from cocoa, together with added sucrose and lipids. All of these can directly or indirectly affect the cardiovascular system by multiple mechanisms. Intervention studies on healthy and metabolically-dysfunctional volunteers have suggested that cocoa improves blood pressure, platelet aggregation and endothelial function. The effect of chocolate is more convoluted since the sucrose and lipid may transiently and negatively impact on endothelial function, partly through insulin signalling and nitric oxide bioavailability. However, few studies have attempted to dissect out the role of the individual components and have not explored their possible interactions. For intervention studies, the situation is complex since suitable placebos are often not available, and some benefits may only be observed in individuals showing mild metabolic dysfunction. For chocolate, the effects of some of the components, such as sugar and epicatechin on FMD, may oppose each other, or alternatively in some cases may act together, such as theobromine and epicatechin. Although clearly cocoa provides some cardiovascular benefits according to many human intervention studies, the exact components, their interactions and molecular mechanisms are still under debate.

Assessment of remineralization potential of Theobromine and Sodium Fluoride gels on Artificial Caries like lesions / Avaliação do potencial de remineralização de géis de teobromina e fluoreto de sódio em lesões de cárie artificial

Objective: To compare the remineralization potential of theobromine and sodium fluoride gels on artificial caries like lesion. Materials and Methods: Forty longitudinal halves of human mandibular premolars were equally divided into 4 groups of 10 samples each: control group (C), samples were stored in distilled water during the experiment period. The remaining 30 specimens were subjected to demineralization protocol to create caries like lesions. samples were immersed for three days in a demineralization solution (pH 5.0) containing 0.2% carbopol and 0.1% lactic acid saturated with calcium phosphate tribasic. The samples were subdivided into 3 equal groups according to the treatment applied during the pH cycle. Demineralization group "D": no treatment applied. Group "F" treated with 2000 mg/liter sodium fluoride gel. Group "T" treated with 200 mg/liter theobromine gel. The specimens of the two studies groups were subjected to Demineralization- Remineralization PH Cycle Protocol for 5 days (Alternating four steps: 1: Treatment material, fluoride or theobromine ˜= 3 minutes. 2: Demineralizing solution 3 hours. 3: treatment material ˜= 3 minutes. 4: Remineralizing solution till the next cycle). The samples were investigated by scanning electron microscope (SEM) and energy dispersive x-ray analysis (EDXA). Results: The enamel of the demineralization group was porous with artificial caries like changes exposing the subsurface enamel rods with severe rod core defects. Theobromine gel and fluoride gel groups showed marked improvement in the surface characteristics in the enamel in both groups. Theobromine gel group showed more observable enamel surface improvement than the fluoride gel group. EDXA revealed that the calcium-phosphorus ratio displayed a descending order: (C > T > F > D). The differences between the two tested groups were not statistically significant. Conclusion: Theobromine gel had more effective remineralizing potential than fluoride gel as a result of its effect in improving the enamel surface characteristics of human teeth. (AU)

Objetivo: Comparar o potencial de remineralização dos géis de teobromina e fluoreto de sódio em lesões de cáries artificiais. Materiais e Métodos: Quarenta metades longitudinais de pré-molares inferiores humanos foram igualmente divididas em 4 grupos de 10 amostras cada: grupo controle (C), as amostras foram armazenadas em água destilada durante o período do experimento. As 30 amostras restantes foram submetidas ao protocolo de desmineralização paracriar lesões artificiais de cárie. As amostras foram imersas por três dias em uma solução de desmineralização (pH 5,0) contendo 0,2% de carbopol e 0,1% de ácido lático saturado com fosfato de cálcio tribásico. As amostras foram subdivididas em 3 grupos iguais, de acordo com o tratamento aplicado durante o ciclo do pH. Grupo de desmineralização "D": nenhum tratamento aplicado. Grupo "F" tratado com 2000 mg / litro de fluoreto de sódio em gel. Grupo & quot;T &q uot; tratado com 200 mg / litro de gel de teobromina. As amostras dos dois grupos de estudo foram submetidas ao protocolo de ciclo de desmineralização - remineralização por 5 dias (quatro etapas alternativas: 1: material de tratamento, flúor ou teobromina ˜= 3 minutos. 2: solução desmineralizante 3 horas. 3: material de tratamento ˜= 3 minutos 4: Solução de remineralização até o próximo ciclo). As amostras foram investigadas por microscopia eletrônica de varredura(MEV) e análise de raios-x dispersivos de energia (EDXA). Resultados: O esmalte do grupo de desmineralização era poroso, com cáries artificiais, como alterações que expunham as hastes de esmalte do subsolo com graves defeitos no núcleo da haste. Os grupos gel de teobromina e flúor apresentaram melhora acentuada nas características da superfície do esmalte nos dois grupos. O grupo gel de teobromina mostrou uma melhoria na superfície do esmalte mais observável do que o grupo gel de fluoreto. A EDXA revelou que a razão cálcio-fósforo exibia uma ordem decrescente: (C> T> F> D). As diferenças entre os dois grupos testados não foram estatisticamente significantes. Conclusão: O gel de teobromina teve um potencial remineralizante mais eficaz que o gel de flúor como resultado de seu efeito na melhoria das características da superfície do esmalte dos dentes humanos. (AU)

Potentiation of the thermogenic antiobesity effects of ephedrine by dietary methylxanthines: adenosine antagonism or phosphodiesterase inhibition?

Current concepts about the mechanisms underlying the therapeutic effects of dietary methylxanthines (caffeine, theophylline, and theobromine) favor their actions as antagonists of adenosine receptors, and attribute their other possible modes of action, namely those associated with translocation of intracellular calcium, inhibition of phosphodiesterase enzyme (PDE) activity, or the release of catecholamines, to high (near-toxic) doses. From studies measuring the respiration rate of brown adipose tissue (BAT), evidence is provided here that at concentrations compatible with therapeutic doses, the ability of methylxanthines (25 to 50 mumol/L) to potentiate the thermogenic effect of the sympathomimetic drug, ephedrine (0.25 mumol/L), particularly under conditions of caloric restriction, involves a minor contribution of adenosine antagonism, but could mainly be explained by the inhibition of PDE activity. In view of current interest in the pharmacological stimulation of metabolic rate to assist the management of obesity with low-calorie regimens, the targeting of PDE activity is therefore a rational approach in the search for drugs that could potentiate sympathomimetic stimulation of metabolic rate.

The intrastratial injection of an adenosine A(2) receptor antagonist prevents frontal cortex EEG abnormalities in a rat model of Huntington's disease.

The influence of 3,7-dimethyl-1-propargylxanthine (DMPX) an adenosine A(2) receptor antagonist, was studied in the quinolinic acid (QA) model of Huntington's disease. Male Wistar rats received bilateral intrastriatal injections of QA (300 nmol) alone or plus DMPX (0.02, 0.2 and 2 microg). At the dose of 0.2 microg, DMPX completely prevented QA-induced EEG abnormalities at the level of frontal cortex. The results support the hypothesis of a neuroprotective role of adenosine A(2) receptor antagonists.

Pentoxifylline, propentofylline and pentifylline for acute ischaemic stroke.

BACKGROUND: Methylxanthine derivatives are vasodilators. They also inhibit platelet aggregation and thromboxane A2 synthesis, decrease the release of free radicals and may be neuroprotective. OBJECTIVES: The objective of this review was to assess the effect of intravenous or oral methylxanthines (pentoxifylline, propentofylline, or pentifylline) in patients with acute ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register, Medline (from 1965), Embase (from 1981), ISI (from 1981) and the Ottawa stroke trials registry. We contacted drug companies. SELECTION CRITERIA: Randomised trials comparing pentoxifylline, propentofylline or pentifylline with placebo or control in patients with definite or presumed acute ischaemic stroke. Trials were included if treatment was started within one week of stroke onset. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied the inclusion criteria. Trial quality was assessed. MAIN RESULTS: Five trials were included. Four trials tested pentoxifylline in 763 people, and one tested propentofylline in 30 people. No trials of pentifylline were found. Early death (within four weeks) occurred in 34 of 408 patients given a methylxanthine drug compared with 49 of 385 given placebo (odds ratio 0.64, 95% confidence interval 0.41 to 1.02). This non-significant trend to less deaths was due mainly to one pentoxifylline trial that found a highly significant reduction in early deaths. Two trials reported early death or disability and found a non-significant reduction (odds ratio 0.49, 95% confidence interval 0.20 to 1.20). Late death (beyond four weeks) was reported in the propentofylline trial involving 30 patients, with no difference between treatment and placebo (odds ratio 0.70, 95% confidence interval 0.13 to 3.68). Data for neurological impairment and disability were not in a form suitable for analysis. Data on quality of life, stroke recurrence, thromboembolism and bleeding were not reported. REVIEWER'S CONCLUSIONS: There is not enough evidence to assess the effectiveness and safety of methylxanthines after acute ischaemic stroke.

Pentoxifylline, propentofylline and pentifylline for acute ischaemic stroke.

BACKGROUND: Methylxanthine derivatives are vasodilators. They also inhibit platelet aggregation and thromboxane A2 synthesis, decrease the release of free radicals and may be neuroprotective. NOTE: This review covers an area where no active research is taking place. It will be updated if relevant information becomes available, e.g. on completion of an appropriate study. OBJECTIVES: To assess the effect of intravenous or oral methylxanthines (pentoxifylline, propentofylline, or pentifylline) in patients with acute ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register (last searched November 2003). For the first version, we also searched EMBASE (1980 to 1999), MEDLINE (1966 to 1999), Science Citation Index (1981 to 1999) and the Ottawa Stroke Trials Registry. We also contacted the manufacturers of methylxanthines and the principal investigators of the identified trials. SELECTION CRITERIA: Randomised trials comparing pentoxifylline, propentofylline or pentifylline with placebo or control in patients with definite or presumed acute ischaemic stroke. Trials were included if treatment was started within one week of stroke onset. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied the inclusion criteria. Trial quality was assessed. MAIN RESULTS: Five trials were included. Four trials tested pentoxifylline in 763 people, and one tested propentofylline in 30 people. No trials of pentifylline were found. The odds of early death (within four weeks) was non-significantly reduced in patients given a methylxanthine drug as compared with those given placebo (odds ratio (OR) 0.64, 95% confidence interval (CI) 0.41 to 1.02). This non-significant trend to less deaths was due mainly to one pentoxifylline trial that found a highly significant reduction in early deaths. Two trials reported early death or disability and found a non-significant reduction (OR 0.49, 95% CI 0.20 to 1.20). There was no significant difference in late death (beyond four weeks), as reported in the propentofylline trial involving 30 patients, although the confidence interval was wide (OR 0.70, 95% CI 0.13 to 3.68). Data for neurological impairment and disability were not in a form suitable for analysis. Data on quality of life, stroke recurrence, thromboembolism and bleeding were not reported. REVIEWERS' CONCLUSIONS: There is not enough evidence to assess adequately the effectiveness and safety of methylxanthines after acute ischaemic stroke.

Cocaine withdrawal severity and urine toxicology results from treatment entry predict outcome in medication trials for cocaine dependence.

Both cocaine withdrawal symptoms, measured by an instrument called the Cocaine Selective Severity Assessment (CSSA), and urine toxicology results obtained at the start of treatment have been shown to predict treatment outcome in outpatient cocaine dependence treatment. This study further evaluates the predictive validity of the CSSA and urine toxicology results, alone and in combination. Subjects included 76 cocaine-dependent individuals who participated in 7-week, outpatient, pilot medication trials for cocaine dependence. Predictor variables included CSSA scores and results from a urine toxicology screen obtained on the first day of medication treatment. Successful outcome was defined as 3 continuous weeks of self-reported abstinence from cocaine confirmed by urine toxicology screens. Predictive validity was assessed by logistic regression analysis. Both the urine toxicology screen and the CSSA scores were significant predictors of 3 weeks of continuous abstinence from cocaine, and the inclusion of both variables significantly improved the predictive validity of either variable alone. Urine toxicology results and CSSA scores obtained at treatment entry are useful predictors of outcome in outpatient cocaine dependence treatment.

SPECT monitoring of improved cerebral blood flow during long-term treatment of elderly patients with nootropic drugs.

PURPOSE: In normal aging persons, oxygen and glucose consumption progressively decreases with reduced cerebral blood flow (CBF), which could be responsible for age-related changes in cognitive functions. A data processing model with the use of Tc-99m SPECT of the human brain has been developed and found to be sensitive for monitoring the effects of drugs that increase CBF. In this study, the effect of two vasodilator drugs (the combination of pentifylline and nicotinic acid versus piracetam) was compared with the effect of placebo on CBF. MATERIALS AND METHODS: Thirty elderly volunteers had three different procedures using the Peelproc method to spatially standardize and compare CBF patterns by SPECT before and after drug intervention. The 30 patients were divided into five groups of six persons each who were randomly assigned in a 1:1 ratio to the treatment sequences consisting of three phases: the combination of pentifylline and nicotinic acid (C), piracetam (N), and placebo (P), or C-N-P; P-N-C; P-C-N; N-C-P; C-P-N; or N-P-C. Phases 1 to 3 each consisted of a baseline recording of parameters (day 0), treatment for 60 days (days 1 to 60), and recording of parameters after treatment (day 61). RESULTS: In elderly human volunteers (ages, 52 to 70 years), after 2 months of oral treatment with a combination of pentifylline and nicotinic acid (800 mg pentifylline, 200 mg nicotinic acid daily), SPECT results for the Peel-proc program indicated a statistically significant improvement in CBF of the total brain, with a more pronounced improvement in the cerebellum and frontal regions, where a definite shift from abnormal to normal blood flow was detected. Spontaneous communication from most of the volunteers suggested that they experienced an improvement in memory and general well-being from the combination treatment. After 2 months of oral treatment with piracetam (2.4 g daily) in elderly human volunteers, SPECT results indicated a regional improvement in CBF, particularly in the cerebellum. However, no beneficial effects with this drug were spontaneously reported. CONCLUSION: The in vivo method to quantitatively monitor the progress of long-term drug therapy on CBF described here could be useful to assess and even direct changes in therapy.