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Biomedical subjects

J Mendoza

Publications and source records attributed to J Mendoza.

At least 37 records · Page 2Linked to original sources
PubMed2000

Maintenance of safer sexual behaviours: evaluation of a theory-based intervention for HIV seropositive men with haemophilia and their female partners.

A theory-based HIV risk-reduction intervention was developed for HIV-positive men with haemophilia and their HIV-negative female romantic partners. The intervention was based on Prochaska and DiClemente's Transtheoretical Model which describes behaviour change as an incremental, stage-based process. The intervention targeted both communication about safer sex and safer sex behaviours (consistent condom use or abstinence from vaginal intercourse). A total of 255 males and 158 females from six funded haemophilia treatment centres or patient organizations (and 27 associated subsites) participated in the study. Baseline and follow-up (15 months after baseline) measures were administered to assess safer sexual behaviours, communication about safer sex and condom self-efficacy. A quasi-experimental, repeated measures design was utilized to compare two naturally occurring groups; those who received the full intervention package and those who received incomplete or no intervention components. Significant intervention effects for safer sex behaviours, communication about safer sex and condom self-efficacy were identified for the male participants, with those receiving the full intervention package demonstrating better outcomes at follow-up. Women who received the full intervention package were more likely to report the use of a condom by their male partner during the last act of vaginal intercourse.

Adult↗
PubMed2000

Inhibition of the mosquito transmission of Plasmodium berghei by Malarone (atovaquone-proguanil).

Sera from patients treated with atovaquone-proguanil (Malarone) have previously been shown to inhibit the mosquito transmission of Plasmodium falciparum, though the inhibition was not complete and the effect declined 2 weeks after treatment. In marked contrast, the inhibition of transmission of P. berghei by human sera (fed to mosquitoes, with P. berghei gametocytes, via membrane feeders) from volunteers treated with atovaquone-proguanil was total up to day 28 post-treatment and still very significant at day 56. In view of the short half-lives of atovaquone and proguanil, this was unexpected, and further experiments, reported here, were undertaken. In contrast to the incomplete blockade of infectivity of P. falciparum by serum taken 4 days post-treatment, such serum was totally inhibitory against P. berghei at a 1:10,000 dilution, indicating a remarkable sensitivity of P. berghei and demonstrating an unusual difference between the two Plasmodium species in response to a drug. The inhibitory effect on P. berghei after day 4 was caused by atovaquone and mainly through blockade of development from ookinete to oocyst. Despite previous information on the rapid elimination of atovaquone by patients, the present data indicate that low concentrations of this drug may persist in the plasma for some weeks after treatment.

Animals↗
PubMed2000

Dependence of anticancer activity of camptothecins on maintaining their lactone function.

Camptothecins contain a lactone ring that exists in the closed form below ph 7. Above 7, the open (CPT+) and the closed (CPT) form coexist in a 50-50 ratio in mouse plasma and in a 90-10 ratio in human plasma due to the high affinity of human serum albumin (HSA) for CPT+. CPT+ is much less toxic than CPT and it is excreted much faster. In complete RPMI 1640 culture medium, the equilibrium CPT(+)-CPT is 50-50. If 4% HSA is added, it moves to 90-10 modeling for the human physiological situation.

Animals↗
PubMed2000

Structure-activity relationship of alkyl camptothecin esters.

The cytotoxicity of camptothecin (CPT) esters 1-6 was measured. Like parental camptothecin, esters 2 and 3, but not 1, 4, 5, and 6, inhibited proliferation of human leukemia cells in culture and induced programmed cell death as assessed by flow cytometry studies. Exhibition of similar levels of antiproliferative activities of CPT 2 and 3 required different incubation time periods in cell cultures, with CPT and 3 requiring the shortest and longest periods, respectively. Both 2 and 3 were inactive against cells resistant to the semisynthetic CPT derivative 9-nitrocamptothecin and unable to stabilize DNA-topoisomerase I (Topo I) "cleavable complexes" in a cell-free system, suggesting that Topo I activity was required but insufficient for the mechanism of action of 2 and 3. Mouse liver homogenate converted esters to parental CPT, but the conversion rates were different with different esters. Of four tested esters in this experiment, ester 2 had the fastest conversion rate. In vivo studies showed that ester 2 had an exceptional lack of toxicity in nude mice, even at enormous doses, and demonstrated extensive activity against human breast and colon tumors grown as xenografts in immunodeficient nude mice, whereas no antitumor activity was observed for the other esters. In conclusion, ester 2 is a prodrug of the antitumor compound CPT, and it can be administered at very high doses in mice with no appearance of toxicity. This study provides a basis for further evaluation of CPT ester 2 as an investigational anticancer agent.

Animals↗
PubMed2000

Pharmacology of camptothecin esters.

An intact lactone ring of camptothecins is a structural requirement for their anticancer activity. Propionate esters of camptothecin (CPT) and 9-nitrocamptothecin (9NC), CZ48 and CZ112, respectively, have been synthesized as derivatives resistant to lactone hydrolysis and are chemotherapeutically active. In this study, we have examined the mechanism of action of CZ48 and CZ112 and their distribution, metabolism, and toxicity. CZ112 incubated in human plasma retained its lactone structure longer than 9NC (t1/2: 10.5 and < 1 hr for CZ112 and 9NC, respectively). This resistance to lactone hydrolysis was also observed in mouse plasma or albumin solutions. Neither CZ48 nor CZ112 inhibit topoisomerase I and thus are prodrugs dependent on hydrolysis to CPT or 9NC, respectively. Rates of hydrolysis of CZ48 to CPT are higher by homogenates of mouse liver, spleen, lung, and kidney than by plasma. Rates of hydrolysis by tumor cells in culture vary and were higher by breast cancer and melanoma cells than by colon cancer cells. On the basis of these and other data, it is proposed that CZ48 and CZ112 may act as anticancer agents by resisting hydrolysis to camptothecins while in circulation. Hydrolysis in tissues may release intact lactone in target tissues.

Animals↗
PubMed2000

[Growth, mortality and exploitation rate of Priacanthus arenatus (Perciformes: Priacanthidae), in the trawl fisheries of northeast Venezuela].

We analyzed growth, mortality and exploitation rate of Priacanhus arenatus, captured by the shrimp trawling fishery (1989-1996), in northeastern Venezuela. The growth coefficient (K) and the asymptotic length (L8) were estimated by length-frequency data using the Battacharya method and other routines of the FISAT program. Total mortality (Z) and exploitation (E) rates were obtained by length-converted catch curve analysis, based on length-frequency data, and the Berverton and Holt's yield per recruit model, respectively. The mean growth parameters L and K were estimated as 474.7 mm and 0.69 year(-1), respectively. Mean total mortality was 4.03 and the exploitation rate range was 0.70-0.80. Results indicated that the population is overexploited.

Animals↗
PubMed1998

Acquisition of cellular resistance to 9-nitro-camptothecin correlates with suppression of transcription factor NF-kappa B activation and potentiation of cytotoxicity by tumor necrosis factor in human histiocytic lymphoma U-937 cells.

Resistance of tumor cells to chemotherapeutic agents is a major problem in cancer therapy. Continuous exposure of human histiocytic lymphoma U-937 cells to 9-nitro-camptothecin (9NC), an inhibitor of the nuclear DNA topoisomerase I, induces resistance to this drug. Because of the involvement of the nuclear factor NF-kappa B in the expression of several growth regulatory genes, we examined the activation of this transcription factor in 9NC-resistant U-937 cells. We found that resistance to increasing concentrations of 9NC correlated with resistance to tumor necrosis factor (TNF)-dependent activation of NF-kappa B. However, the constitutive synthesis of NF-kappa B proteins remained unaffected. Cellular resistance was not unique to TNF, as other activators of NF-kappa B, including interleukin-1, phorbol ester and hydrogen peroxide, also had no effect. There was no difference between 9NC-sensitive and -resistant cells in the activation of NF-kappa B by okadaic acid. Other transcription factors, including AP-1 and Oct-1, were not affected in the resistant cells. When examined for the inhibitory subunit of NF-kappa B (I kappa B alpha), resistant cells showed a faster rate of resynthesis than the control. Interestingly, although 9NC resistance correlated with resistance to TNF-dependent NF-kappa B activation, TNF-dependent cytotoxicity in these cells was enhanced by several hundred fold despite a significant decrease in the number of TNF receptors. In conclusion, our results suggest that NF-kappa B activation may play a role in tumor cell killing by 9NC but not by TNF.

Antineoplastic Agents↗
PubMed1997

Mechanisms of resistance in a human cell line exposed to sequential topoisomerase poisoning.

Camptothecins are a new class of anticancer drugs that target DNA topoisomerase I; current efforts are directed toward elucidating optimal combinations of these drugs with other antineoplastic agents. A rationale for the use of sequential therapy involving the combination of camptothecins with topoisomerase II-targeting drugs, such as etoposide, has arisen from observations of increased topoisomerase II protein levels in cell lines resistant to camptothecin. In an effort to understand potential mechanisms of resistance to this strategy, we developed a U-937 cell subline, denoted RERC, that is capable of surviving exposure to sequential topoisomerase poisoning. The RERC cells are 200-fold resistant to camptothecin, 8-fold resistant to etoposide, and 10-fold hypersensitive to cisplatin compared to the parental U-937 cells. Biochemical analyses indicate that the resistant phenotype involves alterations in both topoisomerase I and topoisomerase IIalpha. Topoisomerase I catalytic activity in the resistant cells is similar to that of the parental line but is resistant to camptothecin. Moreover, the resistant cells express a single mRNA species of topoisomerase I that codes for a mutation in codon 533. In addition, topoisomerase IIalpha protein levels are decreased 10-fold in the resistant line, coincident with a two-fold decrease in the expression of topoisomerase IIalpha mRNA. Collectively, these results indicate that resistance to sequential topoisomerase poisoning may involve a reduction in total cellular topoisomerase activity.

Antineoplastic Agents↗
PubMed1997

Monocytic differentiation of HL-60 promyelocytic leukemia cells correlates with the induction of Bcl-xL.

Treatment of human promyelocytic leukemia HL-60 cells with phorbol esters ultimately induces the differentiation of these cells along the monocyte/macrophage lineage, whereas treatment with retinoic acid or DMSO induces granulocytic/neutrophillic differentiation. In this study, we demonstrate the disparate fates of HL-60 cells treated with the phorbol ester 12,13-phorbol dibutyric acid (PDBu) or DMSO. After DMSO treatment, HL-60 cells eventually died via apoptosis, whereas the viability of PDBu-treated cells was not affected during the same interval. The levels of the apoptosis effector proteins Bak and Bad were enhanced, whereas there was a slight down-regulation of the apoptosis suppressor protein Bcl-2 after treatment of the cells with PDBu and DMSO. Treatment with DMSO resulted in the elevation of the apoptosis effector Bax, whereas treatment with PDBu did not significantly alter the levels of this protein. However, treatment of HL-60 cells with PDBu induced the rapid expression of the apoptosis suppressor protein Bcl-xL, whereas the expression of this protein remained unaltered in DMSO-treated cells. The generality of this finding was confirmed by the induction of Bcl-xL in human myeloid U-937 cells, human peripheral blood monocytes exposed to phorbol ester, and mouse thioglycollate-activated and resident peritoneal macrophages. PDBu-treated HL-60 cells remained viable for 7 days and thereafter began to die via apoptosis, with a concomitant down-regulation of Bcl-xL. In conclusion, we propose that Bcl-xL expression is associated with differentiation and survival of hematopoietic cells along the monocyte/macrophage lineage.

Apoptosis↗
PubMed1997

[Diffuse lung involvement in primary amyloidosis as an infrequent cause of interstitial lung disease. Clinical case].

We report a 50 years old female, admitted to the hospital due to malaise lasting 7 months, with diffuse bilateral lung infiltrates and a progressive respiratory insufficiency, dying one month after admission. A transbronchial biopsy disclosed an extensive amyloid infiltration. The necropsy confirmed this finding and showed a systemic primary amyloidosis associated to a multiple myeloma.

Amyloidosis↗
PubMed1996

An assessment of factors affecting neurological recovery after spinal cord injury with vertebral fracture.

In order to assess some of the variables associated with neurological recovery after traumatic spinal cord injury with vertebral fracture, a randomised sample of 100 patients (50 without neurological recovery, and 50 with several degrees of recovery) were selected out of 245 patients admitted to our hospital. Both groups were homogeneous with respect to time lapse to admission, hospitalization time and level of lesion. Of the variables considered, the intensity of the lesion (incomplete) and vertebral displacement (under 30%) were statistically associated with neurological recovery. An age under 30 years at the moment of the injury was also associated with neurological recovery but only in those patients with an incomplete lesion. No correlation was found between the other variables studied such as the degree of vertebral wedging, type of fracture (compression, flexion-rotation) and management (conservative, surgical) and the neurological evolution.

Adult↗
PubMed1996

[Varicella complicated by pericarditis and pneumonia].

Varicella is a highly infectious disease mainly affecting young children under 14 years of age, and being generally mild. In adults immunodeficient children and neonates exposed in utero, the illness tends to be more severe with higher incidence of complications. The type of complication is linked to the age: in children, bacterial infection of skin lesions and acute cerebellar ataxia are more frequent while lower respiratory tract infection, Reye syndrome and encephalitis are less common. Varicella pneumonia is found typically in adult patients and diffuse encephalitis which course is worse than children could be less frequently. Acute pericarditis is an exceptional complication with a benign course, but only if myocarditis or pericardial effusion are not concurrent. It usually appears in teenagers and young adults; only a few times, it has been linked to other complications as pneumonia or arthritis. We report a varicella case in an adult patient who suffered from pneumonia and pericarditis, both of them were benign.

Acute Disease↗
PubMed1995

Growth inhibition of human cancer metastases by camptothecins in newly developed xenograft models.

Several metastatic models have been developed using clonal selection of human malignant cells metastasizing into a specific organ in NIH-I Swiss immunodeficient mice. The organs of choice were the central nervous system (CNS), targeted by metastases of malignant melanoma, and the liver, with metastases of colon adenocarcinoma. Additional models of adrenal metastases by malignant melanoma, and CNS involvement by implanted human lung squamous carcinoma or lymphoblastoid cells, are also available. Organ metastases, as well as the effects of treatment, were confirmed by autopsies and histological examination of the tissues or by a surgical inspection of the liver. The treatment end points were established as the increases in survival times of treated mice relative to placebo-treated controls. Camptothecins injected i.m. or delivered via gastrointestinal tract inhibit the growth of CNS metastases and increase the survival of treated animals. 9-Amino-20(S)-camptothecin was effective in the CNS model and in the model of liver metastases. The drug increased 3.3- and 5.7-fold the survival rates relative to untreated controls with metastases of colon adenocarcinoma to the liver, and all camptothecins were significantly more effective than 5-fluorouracil, currently a drug of choice in treatment of this disease. The xenograft models of metastases are available for studies of drug passage through the blood-brain barrier optimization of drug delivery to the liver, and for the development of new camptothecin-based treatment strategies.

Adenocarcinoma↗
PubMed1995

Sensitivity of camptothecin-resistant human leukemia cells and tumors to anticancer drugs with diverse mechanisms of action.

Human leukemia U-937 cell clones resistant to 9-nitrocamptothecin (9NC) appear after exposure to increase 9NC-concentrations. Drug resistance is irreversible, regardless of whether the 9NC-resistant (U-937/CR150) cells grow in media with or without 9NC. U-937/CR150 cells are more sensitive than wild type U-937 (U-937/wt) cells to topoisomerase II-directed drugs, amsacrine, daunorubicin, and etoposide. The mitotic inhibitor, vincristine, induces hyperdiploidy in U-937/wt, but not in U-937/CR150 cells, whereas the antimetabolites, cytarabine and methotrexate, and the nitrosourea, carmustine, elicit similar responses in both U-937/wt and U-937/CR150 cells. U-937/CR150-generated tumors in nude mice are sensitive to etoposide. The clinical implications of increased sensitivity of 9NC-resistant tumors to some anticancer drugs are discussed.

Animals↗
PubMed1994

Development of resistance to 9-nitro-camptothecin by human leukemia U-937 cells in vitro correlates with altered sensitivities to several anticancer drugs.

We have recently reported that exposure of human leukemia U-937 cells to progressively increasing concentrations of 9-nitro-camptothecin (9NC) resulted in cell sublines exhibiting various levels of resistance to 9NC. Here, we report responses of wild-type (U-937/wt) and 9NC-resistant (U-937/CR) cells to various anticancer drugs used extensively in cancer chemotherapy. U-937/CR cells were more sensitive than U-937/wt cells to several commonly used drugs of diverse origin including the topoisomerase II-directed drugs amsacrine, etoposide and daunorubicin; the vinca alkaloid vincristine; and the antimetabolite methotrexate. No responses were induced by carmustine in either cell type, whereas similar responses were induced by cytarabine. The sensitivity to the drugs was investigated by monitoring cell proliferation, by determining cell cycle perturbations assessed by flow cytometry analysis of DNA content and by microscopy of stained cells. The results in this report indicate that development of 9NC resistance by the U-937 cells is accompanied by increased sensitivities to other anticancer drugs in vitro and very likely in vivo.

Antineoplastic Agents↗