Octavio Campollo

Antisense S-oligodeoxynucleotides down-regulate TGFβ-production by Kupffer cells from CCl4-injured rat livers

TGFbeta is a pleiotropic cytokine involved in multiple physiological and pathophysiological regulatory mechanisms. Since TGFbeta is a disparate modulator of cell recruitment, proliferation and extracellular matrix phenotype for mesenchymal and nonmesenchymal cells, we have been investigating the role of this cytokine in the pathophysiology of liver. In the present paper we investigate which hepatic cell types from CCl4-injured rat livers express TGFbeta mRNA and produce TGFbeta in culture, with the aim of further obliterating its biological activity by means of antisense technology. We performed a series of comprehensive molecular studies of in situ hybridization, northern blots, and RT-PCR and we found that only non-parenchymal cells produce TGFbeta while its expression in hepatocytes was absent. Consistent with the in situ hybridization findings, we observed that Kupffer cells expressed high steady-state levels of TGFbeta mRNA, while circulating monocytes expressed a smaller amount of TGFbeta transcripts. We did not detect TGFbeta gene expression in endothelial cells. These findings were further confirmed by RT-PCR analyses. TGFbeta activity, as measured by inhibition of [3H]thymidine incorporation by Mv 1 Lu mink lung epithelial cells, was down-regulated in culture by antisense phosphorothioate oligonucleotides. These effects of antisense oligomers were dose-dependent and the sense oligonucleotides had no effect at the same concentration.

Non-injection drug use and hepatitis C among drug treatment clients in west central Mexico

BACKGROUND Research on hepatitis C virus (HCV) prevalence among non-injecting drug treatment clients in the United States, Europe and Asia indicate substantial differences by place. To date, little or no research on HCV and non-injection drug use (NIDU) has been conducted in Mexico. METHODS We examined the prevalence of HCV, hepatitis B virus (HBV), and HIV among non-injecting drug users (NIDUs) in community-based drug treatment (N=122) and NIDUs in a prison-based drug treatment program (N=30), both located in west central Mexico. RESULTS Among the community clients, prevalence was 4.1% (95% confidence interval [CI]: 1.8-9.2) for HCV, 5.7% for HBV (95% CI: 2.8-11.4), and 1.6% for HIV (95% CI: 0.4-5.8). Among the in-prison clients, prevalence was 40.0% (95% CI: 24.6-57.7) for HCV, 20.0% for HBV (95% CI: 9.5-37.3), and 6.7% for HIV (95% CI: 1.9-21.3). None of the clients were aware of being infected. CONCLUSION The HCV prevalence found for the NIDU community treatment clients ranks among the lower HCV estimates published for NIDUs in treatment to date. The prevalence found for the in-prison clients ranks among the higher, raising a concern of possible elevated HCV infection among NIDUs in the west central Mexico prison--one compounded by the finding that none of this studys clients knew they were HCV positive.

DRINKING PATTERNS AND BEVERAGE PREFERENCES OF LIVER CIRRHOSIS PATIENTS IN MEXICO

The purpose of this study was to investigate the pattern of alcoholism in a special group of alcoholics (alcoholic cirrhotics) in a hospital-based population in west central México and assess the role of regional spirits such as tequila. A complete alcohol drinking history and a structured questionnaire directed at investigating the pattern of alcohol consumption was applied to124 adult patients with chronic liver disease caused by alcohol during January1995 to January 1996. The mean age of onset was 27 ± 3 years in women and 18 ± 0.5 years in men. The mean alcohol intake per week was 749 ± 192g for women and 1113 ± 151g for men. On average, patients consumed alcohol for a mean of 24.5 years. The overall patient drinking preference was for tequila followed by 96° Gay Lusac (G.L.), alcohol, and beer. In a subset of 70 patients three phases of alcoholism could be identified (prealcoholic, critical, and chronic). Each phase had a mean duration of at least 11 years.Beer was the dominant beverage in the prealcoholic phase while tequila was consumed more often in the other phases. In the critical phase of alcoholism an average of 337g of alcohol were consumed per week and in the chronic phase1765g/week. Tequila was the overall preferred beverage in this group of alcoholics.Other beverages included beer and straight alcohol with a clear trend from less to higher concentration of alcohol throughout the drinking history. Subtle gender differences in the patterns of alcoholism may be suspected. In this group of patients the role of tequila drinking is highlighted.

Mexico's precursor chemical controls: Emergence of less potent types of methamphetamine in the United States

BACKGROUND This study examines whether Mexicos controls on ephedrine and pseudoephedrine, the two precursor chemicals that yield the most potent form of methamphetamine, d-methamphetamine, impacted the prevalence/availability of less potent types of methamphetamine in the United States-types associated with the alternative precursor chemical P2P. METHOD Using ARIMA-intervention time series analysis of monthly drug exhibits (a prevalence/availability indicator) from the System to Retrieve Information from Drug Evidence (STRIDE), we tested whether Mexicos controls, which began in 2005, were associated with growth/decline in d-methamphetamine and growth/decline in P2P-associated, less potent l-methamphetamine, racemic methamphetamine (a 50:50 ratio of d- and l-isomers), and mixed isomer methamphetamine (an unequal ratio of d- and l-isomers). Heroin, cocaine and marijuana exhibits were used for quasi-control (01/2000-04/2011). RESULTS Mixed-isomer exhibits constituted about 4% of the methamphetamine exhibits before Mexicos controls, then rose sharply in association with them and remained elevated, constituting about 37% of methamphetamine exhibits in 2010. d-Methamphetamine exhibits dropped sharply; l-methamphetamine and racemic methamphetamine exhibits had small rises. d-Methamphetamine exhibits partially recovered in the US West, but little recovery occurred in the US Central/South. Quasi-control series were generally unaffected. CONCLUSION The US methamphetamine market changed. Widespread emergence of less potent methamphetamine occurred in conjunction with Mexicos controls. And prevalence/availability of the most potent type of the drug, d-methamphetamine, declined, a partial recovery in the West notwithstanding. Granting that lower potency drugs typically engender less dependence and attendant problems, these findings suggest that, following Mexicos controls, the potential harm of a sizeable amount of the US methamphetamine supply decreased.

High frequency of the DRD2/ANKK1 A1 allele in Mexican Native Amerindians and Mestizos and its association with alcohol consumption

BACKGROUND Mexico has an ancient tradition of alcohol drinking influenced by genetic and sociocultural factors. This study aimed to determine the distribution of the DRD2/ANKK1 TaqIA polymorphism in Mexican populations and to analyze its association with heavy drinking. METHODS In a cross-sectional and analytical study, 680 unrelated subjects including two Native Amerindians groups (87 Nahuas and 139 Huicholes), and two Mestizos groups (158 subjects from Tepic, Nayarit and 296 subjects from Guadalajara, Jalisco) were enrolled. DRD2/ANKK1 genotyping was performed by PCR-RFLP and allelic discrimination assays. Genetic analyses were conducted by Arlequin and Structure software. Heavy drinking was defined as ≥300g alcohol/week. The association of the DRD2/ANKK1 TaqIA polymorphism with heavy drinking was estimated. RESULTS Heavy drinking was prevalent in 64.7% of the study population. The DRD2/ANKK1 A1 allele prevailed in 67% and 65% of Nahuas and Huicholes, respectively and 51% and 47.3% in Mestizos from Tepic and Guadalajara, respectively. Heavy drinking was associated with the A1A1 genotype in the Mestizos of Guadalajara (A1A1 vs. A1A2 OR=4.79, 95%CI 1.81-12.68, p=0.0006; A1A1 vs. A1A2+A2A2, OR=4.09, 95%CI 1.56-10.68, p=0.0021) and in the Mestizos from Tepic (A1A1 vs. A1A2, OR=5.92, 95%CI 2.12-16.49, p=0.0002); A2A2, OR=14.56, 95%CI 3.57-59.24, p=0.00004); A1A2+A2A2, OR=6.68, 95%CI 2.42-18.42, p=0.00005). In Native Amerindians, a lack of association was found. CONCLUSIONS High frequencies of the DRD2/ANKK1 A1 allele were present in Mexican populations. Native Amerindians exhibited the highest frequencies of the A1 allele documented worldwide to date. The A1A1 genotype was associated with heavy drinking in Mestizos.

A novel sodium benzoate analog (CH-1) decreases blood ammonia levels in experimental hyperammonemia

Sodium benzoate has been used for the treatment of congenital hyperammonemic syndromes and hepatic encephalopathy for its ammonia lowering effect. A zinc-derivative of sodium benzoate (CH-1) with similar effects, is presented herein. We administered CH-1 at doses of 250, 500 and 1000 mg/kg body weight during 7 days to male Wistar rats after a portocaval shunt operation was performed as a model for experimental hyperammonemia. There was a decrease in blood ammonia levels in all groups receiving CH-1. A linear relationship (r=−0.487, P<0.01) was observed between the dose of CH-1 and blood ammonia levels. The effective dose 50 (ED50) was 320 mg/kg body weight (95% C.I. 176–581 mg) with a slope of 1.538 (Litchfield and Wilcoxon method). These results suggest that benzoic acid salts such as CH-1 may prove a new alternative for the treatment of hyperammonemia. Potential advantages of non-sodium salts of benzoic acid are discussed.