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Biomedical subjects

R Bojalil

Publications and source records attributed to R Bojalil.

At least 19 recordsLinked to original sources

Anti-tumor necrosis factor alpha F(ab')2 antibody fragments protect in murine polymicrobial sepsis: concentration and early intervention are fundamental to the outcome.

BACKGROUND: Negative results are frequent using anti-TNFalpha antibodies in sepsis models and clinical trials. METHODS AND RESULTS: Different prophylactic doses of anti-TNFalpha F(ab')2 antibody fragments were compared for the prevention of death by sepsis induced by cecal ligation and puncture (CLP) in mice. High (10 mg/kg) and very low (0.01 and 0.1 mg/kg) concentrations of anti-TNFalpha antibody fragments were not the most adequate for treating polymicrobial sepsis, since they did not significantly improve survival. To the contrary, intermediate doses (1 mg/kg) significantly protected the challenged animals. Protective activity was also observed when administration of the antibody fragments was initiated early (up to 30 min) after CLP. CONCLUSIONS: These results suggest that in processes where excessive production of cytokines is involved, the aim should be to return them to their physiologically acting range but not to inhibit their production. The timing of initiating therapy should also be considered in order to maximize the possible benefits.

Animals↗

Mechanical deformation inhibits IL-10 and stimulates IL-12 production by mouse calvarial osteoblasts in vitro.

The skeleton is continuously remodelled throughout life, a process that is orchestrated by cells of the osteoblast lineage. Remodelling involves a complex network of cell-cell signalling involving systemic hormones, locally produced cytokines, growth factors and the mechanical environment of the cells. Here, we report on the effect of mechanically-induced strain on the synthesis by mouse calvarial osteoblasts in monolayer culture of IL-10 and IL-12, two cytokines that inhibit osteoclast formation in bone marrow cultures; IL-10 also suppresses osteoblast differentiation suggesting a role for both cytokines in bone physiology. A tensile strain was applied to the cells intermittently for 6s, every 90s, for 2-96h. After 2-h culture, supernatants from deformed cells contained significantly less IL-10 than control cultures. In contrast, mechanical deformation had a stimulatory effect on IL-12 synthesis; however, by 48h both had returned to control levels. These data suggest that IL-10 and IL-12 can be added to the growing list of mechanical stress-responsive genes. The down-regulation of IL-10 and stimulation of IL-12 further suggests that the initial response of the cells to mechanical deformation was an osteogenic one.

Animals↗

CD4+ TCRalphabeta T cells are critically involved in the control of experimental murine cysticercosis in C57BL/6J mice.

Taenia crassiceps cysticerci develop in the peritoneal cavity of BALB/cAnN mice and, to a lesser extent, in C57BL/6J mice. The mechanisms involved in the immunity to this murine cysticercosis seem to be mainly mediated by T cells. To gain further insight into the mechanisms of cysticercal immunity, the susceptibility of mice deficient in different immunologically relevant genes was compared with that of the respective wild type. Mice were classified according to the parasite load and survival after infection: highly susceptible (HS), with an increased parasite load and mortality rate (CD4-/-, TCRalpha-/-, TCRbeta-/-, RAG1-/-), susceptible, with only increased parasite load (TCRdelta-/-, BALB/cAnN), and relatively resistant, with a lower number of parasites (CD8-/-, WT). Neither specific proliferative response nor Th2 cytokine or antibody responses were observed in HS mice. These data strongly suggest that CD4+TCRalphabeta+ T cells have a critical role in the control of T. crassiceps murine cysticercosis.

Animals↗

The impact of a clinical training unit on integrated child health care in Mexico.

This study had two aims: to describe the activities of a clinical training unit set up for the integrated management of sick children, and to evaluate the impact of the unit after its first four years of operation. The training unit was set up in the outpatient ward of a government hospital and was staffed by a paediatrician, a family medicine physician, two nurses and a nutritionist. The staff kept a computerized database for all patients seen and they were supervised once a month. During the first three years, the demand for first-time medical consultation increased by 477% for acute respiratory infections (ARI) and 134% for acute diarrhoea (AD), with an average annual increase of demand for medical care of 125%. Eighty-nine per cent of mothers who took their child for consultation and 85% of mothers who lived in the catchment area and had a deceased child received training on how to recognize alarming signs in a sick child. Fifty-eight per cent of these mothers were evaluated as being properly trained. Eighty-five per cent of primary care physicians who worked for government institutions (n = 350) and 45% of private physicians (n = 90) were also trained in the recognition and proper management of AD and ARI. ARI mortality in children under 1 year of age in the catchment area (which included about 25,000 children under 5 years of age) decreased by 43.2% in three years, while mortality in children under 5 years of age decreased by 38.8%. The corresponding figures for AD mortality reduction were 36.3% and 33.6%. In this same period, 11 clinical research protocols were written. In summary, we learned that a clinical training unit for integrated child care management was an excellent way to offer in-service training for primary health care physicians.

Child↗

Th1-type cytokines improve resistance to murine cysticercosis caused by Taenia crassiceps.

Resistance and susceptibility to different parasitic diseases have been associated with the predominance of Th1- or Th2-type immune responses. In experimental murine cysticercosis a Th1 response seems to be involved in resistance, whereas Th2 activity is associated with heavy parasite intensities. To test this notion the roles of Th1- and Th2-type cytokines in infected mice were studied after treatment with anticytokine monoclonal antibodies or with recombinant murine cytokines during early stages of infection. Mice receiving anti-interleukin 10 (IL-10) carried lower parasite intensities than did control mice and developed a strong Th1-type response, whereas mice receiving anti-interferon gamma (IFN-gamma) showed a dramatic increase in susceptibility. Treatment with recombinant cytokines confirmed these results; mice receiving IFN-gamma and IL-2 showed low parasite numbers, whereas IL-10 induced a significant increase in parasite loads. Thus, the Th1-type immune response plays a fundamental role in protection against Taenia crassiceps cysticercosis, whereas Th2, at least through IL-10, favors parasite establishment.

Animals↗

Taenia crassiceps cysticercosis: a role for prostaglandin E2 in susceptibility.

Several biological factors are involved in susceptibility and resistance to murine cysticercosis. A substantial body of evidence implies prostaglandins as potent regulators of immune responses during parasitic diseases. Here we evaluated the role played by prostaglandin E2 in cysticercosis. Mice were treated in vivo with prostaglandin E2 or with indomethacin (a prostaglandin E2 synthesis inhibitor) before infection. Parasite growth was enhanced by prostaglandin treatment, which provoked poor Con-A responses, low Th1-type cytokines secretion, and high levels of IL-6 and IL-10. In contrast, mice receiving indomethacin showed a reduction in parasite load parallel to a strong Con-A response and high levels of IL-2 and IFN-gamma, concomitantly with a decrease in IL-4, IL-6 and IL-10 production. Indirect in vitro studies suggest that an important source of prostaglandin E2 production could be related to host's adherent cells. However, prostaglandin E2 from parasite origin cannot be discarded.

Animals↗

Susceptibility to Trypanosoma cruzi is modified by a previous non-related infection.

Helminth infections are frequently massive, chronic and strong inductors of Th2-type cytokines. This implies that infection by such parasites could alter the susceptibility to subsequent infections by other pathogens, particularly intracellular parasites. We therefore explored whether a persistent infection, caused by Taenia crassiceps cysticerci, in BALB/c mice could affect susceptibility to a later infection by Trypanosoma cruzi. We found that the presence of the cysticerci indeed modified the immune response and the susceptibility to T. cruzi, and that these modifications depended on the time-course evolution of the initial infection. Coinfection with the protozoan in the early stages of the helminth infection, induced a delay on the onset of parasitaemia, early specific production of IFN-gamma and high specific production of IL-4. A significant increase in susceptibility to T. cruzi was observed only when mice were coinfected in late stages when the helminth load is greater and a Th2 type response against it is predominant. The in vitro specific response to T. cruzi antigens was then characterized by low levels of both IFN-gamma and IL-4. These findings suggest that chronic helminth infections could potentially have a significant influence over the immune response and hence susceptibility to other pathogens.

Animals↗

A clinical training unit for diarrhoea and acute respiratory infections: an intervention for primary health care physicians in Mexico.

In Tlaxcala State, Mexico, we determined that 80% of children who died from diarrhoea or acute respiratory infections (ARI) received medical care before death; in more than 70% of the cases this care was provided by a private physician. Several strategies have been developed to improve physicians' primary health care practices but private practitioners have only rarely been included. The objective of the present study was to evaluate the impact of in-service training on the case management of diarrhoea and ARI among under-5-year-olds provided by private and public primary physicians. The training consisted of a five-day course of in-service practice during which physicians diagnosed and treated sick children attending a centre and conducted clinical discussions of cases under guidance. Each training course was limited to six physicians. Clinical performance was evaluated by observation before and after the courses. The evaluation of diarrhoea case management covered assessment of dehydration, hydration therapy, prescription of antimicrobial and other drugs, advice on diet, and counselling for mothers; that of ARI case management covered diagnosis, decisions on antimicrobial therapy, use of symptomatic drugs, and counselling for mothers. In general the performance of public physicians both before and after the intervention was better than that of private doctors. Most aspects of the case management of children with diarrhoea improved among both groups of physicians after the course; the proportion of private physicians who had five or six correct elements out of six increased from 14% to 37%: for public physicians the corresponding increase was from 53% to 73%. In ARI case management, decisions taken on antimicrobial therapy and symptomatic drug use improved in both groups; the proportion of private physicians with at least three correct elements out of four increased from 13% to 42%, while among public doctors the corresponding increase was from 43% to 78%. Hands-on training courses thus seemed to be effective in improving the practice of physicians in both the private and public sectors.

Acute Disease↗

The quality of private and public primary health care management of children with diarrhoea and acute respiratory infections in Tlaxcala, Mexico.

In Tlaxcala, Mexico, 80% of the children who died from diarrhoea or acute respiratory infections (ARI) in 1992-1993 received medical care; in more than 70% of cases it was provided by a private general practitioner (GP). The present study evaluated the quality of case management by private and public GPs to children under five years of age with diarrhoea and ARI. During the clinical observation, the treatment and counselling given to the mother were assessed with the WHO guidelines as reference standard. A total of 41 private and 40 public GPs were evaluated for the management of diarrhoea, and 59 private and 40 public GPs for the management of ARI. For diarrhoea, half of the private GPs gave inadequate rehydration therapy, 63% gave incorrect advice on diet, 66% and 49% made an incorrect correct decision in the prescription of antimicrobial and symptomatic drugs, respectively. Public GPs generally performed better in diarrhoea management: 7% gave inadequate rehydration therapy, 13% gave wrong advice on diet, 3% made a wrong decision in the prescription of symptomatic drugs and 28% gave a wrong decision in antimicrobial prescription. In the management of ARI, 66% and 58% of private GPs made a wrong decision in the prescription of antimicrobial and symptomatic drugs, respectively, compared to 30% and 20% of public GPs, respectively. Counselling to the mother given by both private and public GPs was considered inadequate in most cases of diarrhoea and ARI. These results clearly show that private doctors, as important providers of medical care, need to be included in the strategies to improve the quality of care of children with diarrhoea and ARI. Future research needs to address the determinants of the clinical practice of private doctors in countries like Mexico.

Child↗

Shift from an early protective Th1-type immune response to a late permissive Th2-type response in murine cysticercosis (Taenia crassiceps).

In early stages of experimental murine cysticercosis caused by Taenia crassiceps, there is a clear but transient Th1-type immune response (characterized by high levels of interleukin [IL]-2, interferon-gamma, concanavalin A, and antigen specific response, delayed-type hypersensitivity, and immunoglobulin [Ig]G2a antibodies) that associates with a low rate of parasite reproduction. As time of infection progresses an energic and more permanent Th2-type response follows (characterized by high levels of IL-4, IL-6, IL-10, IgG2b, and IgG1 antibodies) that in turn associates with an increment in the rate of parasite reproduction. The sequential activation of Th1-type and Th2-type responses in murine cysticercosis would appear to favor progressively parasite reproduction, explaining the long time residence and the massive parasite intensity reached in chronic infections.

Animals↗

Antibiotic use in a periurban community in Mexico: a household and drugstore survey.

In developing countries, antibiotics are the most common drugs sold, and some data suggest that they are frequently misused. In order to describe the pattern of antibiotic use in a periurban community in Mexico City, 1659 randomly-selected households were visited and an interview with the housewife was carried out. Six local drugstores also were selected at random. A social worker made six visits to each pharmacy, observed the events during the purchase of the drug and applied a structured questionnaire to the customer immediately after the transaction. Of 8279 individuals, 425 (5%) said that they had used at least one antimicrobial in the preceding 2 weeks and antibiotics were the majority (29%) of the drug sales. The main perceived reasons for drug use were acute respiratory tract ailments and gastroenteritis. Interviewees reported that antibiotic therapy was given in 27% of respiratory diseases and in 37% of all diarrheal episodes. The drugs most commonly reported were: penicillins, erythromycin, metronidazole, neomycin, cotrimoxazole and tetracyclines. While self-medication and drug purchases without medical prescription were common, the majority of antibiotics were prescribed by a physician. Approximately two thirds of individuals using an antibiotic said they had used it for less than 5 days and 72% of the purchases were for insufficient quantities of drugs. Our data suggest that antibiotics are frequently misused and they support the need to assess the determinants of self-medication, health-seeking behavior and physician prescribing practices. The need for effective educational programs to improve prescribers' decisions is stressed.

Adolescent↗

Antibiotic misuse in diarrhea. A household survey in a Mexican community.

A survey of 1659 households in a periurban community in Mexico City was carried out to assess the frequency of and risk factors for inappropriate antimicrobial therapy in acute diarrhea. The housewife was interviewed to obtain information of the occurrence of diarrhea or use of an antibiotic in the previous 2 weeks by any member of the family. An antibiotic was used in 37% or 287 diarrheal episodes although only in 5% of all episodes was this therapy indicated, based on the presence of gross blood in stools. Patients seen by a physician were 6 times more likely to be treated with an antibiotic compared to those who did not consult a physician (p < 0.001). Self-medication was associated with a higher risk of using an inadequate drug or dose (in 72% of treated episodes) and of following treatment for less than 5 days (in 66% of treated episodes). Other risk factors significantly and independently associated with antibiotic misuse were: an increased number of stools (odds ratio [OR] = 1.21; 95% confidence interval [CI] = 1.04, 1.41), bloody diarrhea (OR = 19.04; 95% CI = 2.52, 160.90) and family crowding (OR = 2.07; 95% CI = 1.17, 3.63). These findings support future community-oriented educational interventions aimed at improving physician prescribing practices and patient compliance behavior in order to achieve a more rational use of antibiotics.

Acute Disease↗

A role for 17-beta-estradiol in immunoendocrine regulation of murine cysticercosis (Taenia crassiceps).

In experimental murine cysticercosis caused by Taenia crassiceps, parasite reproduction is favored by thymectomy or by orchidectomy, and restricted by ovariectomy. Hormonal reconstitution experiments showed that 17-beta-estradiol increases parasite numbers whereas 5-alpha-dihydrotestosterone was ineffective. Parasite numbers decreased with increments in cellular immunity but were insensitive to antibody levels. A possible immunoendocrinological interaction involving estrogen as a depressor of cellular immunity is envisaged in the control of cysticercosis.

Animals↗

[The use of antibiotics in a community of Mexico City. I. A household survey].

Based on previous community-oriented studies an irrational use of antibiotics, particularly in developing countries, has been suggested. In order to describe the pattern of antibiotic use in a periurban community in Mexico City, 1659 randomly selected households were visited and an interview to the housewife was carried out. Of 8279 individuals 425 (5%) had used at least one antimicrobial in the preceding two weeks. Main perceived reasons for drug use were: respiratory tract ailments (58%) and acute diarrhea (25%). Antibiotic therapy was given in 27% of respiratory diseases and in 37% of all diarrheal episodes. Most commonly used drugs were: penicillins (43%), erythromycin (13%), metronidazole (9%), neomycin (6%), cotrimoxazole (6%) and tetracyclines (6%). While self-medication was common (19%) the majority of antibiotics were prescribed by a physician (81%). Approximately two thirds of individuals using an antibiotic did it for less than five days. Our data suggest a frequent misuse of antibiotics and support the future assessment, in this community, of physician prescribing practices, the determinants of self-medication as well as the impact of this drug use on the selection of resistant bacterial strains.

Adolescent↗

[Antibiotic consumption in a community of Mexico City. II. Survey of purchases at pharmacies].

In developing countries, antibiotics are the most common sales of drugs and it has been suggested that their irrational use leads to the emergence of resistant bacteria. In order to assess the purchase of antimicrobials in a peri-urban community in Mexico City six local drug stores were randomly selected. A social worker made five visits to each pharmacy and she observed the events during the purchase of the drug and applied a structured questionnaire to the customer immediately after the transaction. Antibiotics were the majority (29%) of the drug sales. Of all purchasers of an antibiotic 43% did it without medical prescription and 72% answered that a physician had influenced on the purchase. Duration of the antibiotic therapy was specified in one out of three prescriptions that were examined and only in 28% of the sales the purchase was enough for a treatment duration of more than four days. More information, from similar surveys in drug stores in other settings, is needed to support the reinforcement of actions to control the sales of antibiotics in the community.

Anti-Bacterial Agents↗

Thymus-related cellular immune mechanisms in sex-associated resistance to experimental murine cysticercosis (Taenia crassiceps).

The role of sex, thymus, and cellular immune mechanisms in mouse resistance to experimental cysticercosis with Taenia crassiceps was studied in male and female susceptible mice treated with cyclophosphamide, as well as in mice neonatally thymectomized and passively transferred with T-enriched lymphoid cells. High doses of cyclophosphamide increased delayed hypersensitivity and resistance of mice of both sexes without affecting antibody production. Neonatal thymectomy diminished resistance in both sexes but depressed delayed hypersensitivity in females only, without significantly affecting antibody response in either sex. Passive transfer of T-enriched lymphoid cells to thymectomized mice restored resistance to control levels without greatly affecting delayed hypersensitivity. Thus, our results indicate that cell-associated immune mechanisms are implicated in resistance to murine cysticercosis with T. crassiceps. Because neonatal thymectomy nearly equalized the intensity of infection of female and male mice, it is argued that the thymus is importantly involved in the interaction between gonads and the immune system in the control of this cysticercosis.

Animals↗

Low risk of invasive amebiasis in cyst carriers. A longitudinal molecular seroepidemiological study.

A seroepidemiological study of a household cohort, using both clinical observational and molecular criteria was conducted in a periurban area endemic for E. histolytica infection. This longitudinal study was undertaken to determine the risk of asymptomatic cyst carriers to develop invasive illness. Zymodeme patterns of strains isolated from these patients were correlated both with the clinical presentation of disease and with the serological response against the M-17 ameba antigen and further compared with that found in 16 proven cases of amebic liver abscess. From a total of 163 housewives screened, 39, (24%) were asymptomatic cyst carriers; 31 of them (index cases) and 114 members of their households remained in the study over an 8 month follow-up period to detect ameba infection and illness. Of the household members at risk, 46 (40%) became infected within 6 weeks. None of the index or secondary cases developed ameba-related symptoms and cyst excretion followed a chronic persistent, intermittent, or transient pattern over the period of the study. Amebas were recovered and zymodemes determined in 19 of 71 (27%) cyst carriers. Ameba shed from each of these 19 carriers exhibited nonpathogenic zymodeme 1, except for one index case where zymodeme 2 was recovered in one sampling, and returned to zymodeme 1 in subsequent samples. Of 48 of 71 cyst carriers studied, antibodies to crude E. histolytica antigen were detected by ELISA in 16 (31%); antibodies to the M-17 fusion protein were found in 8 (16%) by ELISA and in 2 (4%) by Western-Blot (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗