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Preface@#The Clinical Practice Guidelines (CPG) for the Diagnosis and Management of Pediatric Community-Acquired Pneumonia (PCAP) was initiated by the Philippine Academy of Pediatric Pulmonologists, Inc. (PAPP) and the Pediatric Infectious Disease Society of the Philippines (PIDSP), in cooperation with Philippine Pediatric Society, Inc. (PPS) way back in 2004. Several CPG updates were then undertaken by the PAPP PCAP CPG Task Force from 2008 to 2016. Clinically-relevant research questions were answered with recent and current recommendations based on evidence from local and international data. The 2021 PCAP CPG initiative was envisioned in March 2018 upon the recommendations of the 2018 PAPP Board for the purpose of updating the evidence in the PCAP CPG 2016 clinical questions. This led to the collaboration of PAPP and PIDSP to develop this CPG. Individual members were identified from each society as content experts to form the Steering Committee along with a clinical epidemiologist and technical writer as review experts. The committee identified the scope and target end user of the CPG as well as additional clinical questions to be included in the 2021 update aside from the questions on the previous CPGs. Selected members from the two societies formed the Technical Working Group (TWG) who did the literature search, appraisal of evidences, and formulation of recommendations. These recommendations were then presented to the stakeholders who became part of the consensus panel. There was no identified conflict of interest among the CPG developers, TWG members and stakeholders. A survey to determine potential competing interests were conducted during the development of this CPG. This initiative was fully funded by the PAPP and PIDSP societies. The 2021 PCAP CPG significantly differs from the previous CPGs in several aspects. First, the current guideline is a consensus between two pediatric societies. Second, much of the literature review has been centered on meta-analyses or systematic reviews instead of individual studies. Finally, appraisal of published literature was based on Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria. Such methodological differences may provide difficulties in defining evolution of care through the years. As identified in the previous CPG updates, there is lack of local data hence most of the evidences gathered came from international studies. The applicability of such data to the local setting needs to be critically assessed for its value and relevance. Corollary to this, several gaps in knowledge are identified and these may serve as a guide for future research.

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Large-scale propagation of oil palm (Elaeis guineensis, Jacq.) is difficult due to its single apical meristem. Thus, obtaining plants is mainly through seed germination, and a long growing period is required before oil production is possible. An alternative to large-scale seedling production is indirect somatic embryogenesis. The aim of this study was to analyze the somatic embryogenesis process in oil palm (E. guineensis Jacq.) with amino acids and low concentrations of auxins. The Tenera hybrid was analyzed by cytochemical and ultrastructural methods and was used to regenerate oil palm plants. First, calli were induced in MS culture media supplemented with 2,4-D and picloram. Two types of calli were obtained, characterized by beige or translucent color. Beige calli had embryogenic characteristics, such as large nuclei with prominent nucleoli, and they were multiplied for 8 months in MM culture (half strength MS, 1 mg L-1 2,4-D, 2 mg L-1 2iP, 1 mg L-1 IBA, 250 mg L-1 citric acid, 10 mg L-1 cysteine, 100 mg L-1 inositol, 1 mg L-1 thiamine, 1 mg L-1 pyridoxine, 1 mg L-1 nicotinic acid, 1 mg L-1 glycine, 200 mg L-1 malt extract, and 100 mg L-1 casein hydrolysate). After multiplication, the MCB culture medium (half strength MS, supplemented with 0.25 mg L-1 NAA, 2 mg L-1 BAP, MM vitamins and 200 mg L-1 malt extract, and 100 mg L-1 casein hydrolysate) was the most efficient for embryo formation, showing meristematic centers with totipotent cells in histochemical analyses. The somatic embryos were developed and germinated in MG medium (half strength MS, 0.45 mg L-1 IAA, 0.25 mg L-1 BAP, and MM vitamins), transplanted into polyethylene tubes containing pine bark substrates, and acclimatized in a greenhouse, achieving a 97% survival rate. The use of picloram for callus induction and somatic embryogenesis is advantageous and multiplication in MM medium is an important step for increasing cell mass. The calli with light beige color and nodular structures have meristematic cells with dense cytoplasm and totipotential features that later give rise to protoderm, procambium, and ground meristem during the globular, cordiform, and torpedo embryogenesis phases. In MCB medium, the concentration of vitamins and amino acids are crucial for somatic embryogenesis.

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Infiltration of renal parenchyma by neoplastic plasma cells in myeloma patients is an unusual finding. We report 3 cases of myeloma, with renal biopsy being the first clue to the diagnosis in one. The plasma cell infiltrate in other two cases was not so evident but immunofluorescence (IF) and immunohistochemical (IHC) stains for light chains helped establish the monoclonal nature of the infiltrate. We surmise that plasma cell infiltration in the kidney can be an important clue to the diagnosis of an underlying myeloma and could in future be regarded as a myeloma-defining event (MDE) if monoclonality is confirmed. This finding could directly affect the prognosis and be a direct indicator of the tumor burden. Further studies are however required to determine the exact prognostic value and precise relationship of such a finding with deranged renal functions in myeloma.

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Nephrotic syndrome can be rarely due to inherited disorders of enzymes. One such variety is lecithin cholesterol acyltransferase deficiency. It leads to accumulation of unesterified cholesterol in the eye and other organs. We report a case of nephrotic syndrome with cloudy cornea and hypocholesterolemia with foam cells and lipid deposits on renal biopsy. Awareness about this rare disease may help in the early institution of specific measures to prevent progression to end-stage renal disease.

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Several antineoplastic drugs have been classified as carcinogens by the International Agency for Research on Cancer (IARC) on the basis of epidemiological findings, animal carcinogenicity data, and outcomes of in vitro genotoxicity studies. 5-Fluorouracil (5-FU), which is easily absorbed through the skin, is the most frequently used antineoplastic agent in Portuguese hospitals and therefore may be used as an indicator of surface contamination. The aims of the present investigation were to (1) examine surface contamination by 5-FU and (2) assess the genotoxic risk using cytokinesis-block micronucleus assay in nurses from two Portuguese hospitals. The study consisted of 2 groups: 27 nurses occupationally exposed to cytostatic agents (cases) and 111 unexposed individuals (controls). Peripheral blood lymphocytes (PBL) were collected in order to measure micronuclei (MN) in both groups. Hospital B showed a higher numerical level of contamination but not significantly different from Hospital A. However; Hospital A presented the highest value of contamination and also a higher proportion of contaminated samples. The mean frequency of MN was significantly higher in exposed workers compared with controls. No significant differences were found among MN levels between the two hospitals. The analysis of confounding factors showed that age is a significant variable in MN frequency occurrence. Data suggest that there is a potential genotoxic damage related to occupational exposure to cytostatic drugs in oncology nurses.

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An evaluation of the electrocardiographic profile of 50 clinically healthy Quarter Horses, with ages ranging from six months to 28 years old, 34 females and 16 males, was performed. Heart rate has not decreased with age, and duration of the QRS complex increased with the growth of the animal. The amplitude of the S and T1 waves were higher in male subjects than in female Quarter Horses.

Avaliou-se o perfil eletrocardiográfico de 50 equinos da raça Quarto de Milha, clinicamente sadios, com idades variando de seis meses a 28 anos, sendo 34 fêmeas e 16 machos. A frequência cardíaca não diminuiu com a idade, e a duração do complexo QRS aumentou ao longo do crescimento do animal. A amplitude das ondas S e T1 foram maiores nos indivíduos machos do que nas fêmeas da raça Quarto de Milha.

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Avaliaram-se a incidência de endometrite citológica dos 29 aos 90 dias pós-parto e seus efeitos sobre o desempenho reprodutivo de vacas de corte Nelore submetidas a uma estação de monta (EM) de 90 dias. Foram utilizadas 49 matrizes Nelores, sem histórico de retenção de placenta, sem a presença de uma infecção uterina clínica, e com escore de condição corporal acima de 2,5. Realizou-se exame ultrassonográfico para avaliar a parede uterina e a atividade ovariana. O diagnóstico de endometrite citológica foi feito pela técnica de lavagem uterina, considerando-se caso de endometrite ≥5% de neutrófilos em cada lâmina. A incidência de endometrite citológica do rebanho foi de 22%, não diferindo entre as categorias analisadas (primíparas versus multíparas) (P>0,05), a taxa de concepção à primeira inseminação também foi semelhante entre primíparas versus multíparas (P>0,05), porém a taxa de gestação ao final da EM foi maior nas vacas multíparas (83,8%) quando comparadas às primíparas (50,0%) (P<0,05). A presença ou ausência da endometrite citológica não influenciou a taxa de concepção (P>0,05), tampouco a taxa de gestação ao final da EM (P>0,05). Conclui-se que o uso da citologia endometrial não se justifica como ferramenta de diagnóstico em vacas de corte Nelore.

Were evaluated the incidence of cytological endometritis from 29 to 90 days postpartum and its effect on the reproductive performance of Nelore beef cows submitted to a breeding season (BS) for 90 days. A total of 49 cows, with no history of retained placenta, without the presence of a clinic uterine infection, and with a body condition score above 2.5 were used. Ultrasound examination was performed to evaluate the uterine wall and ovarian activity. The cytological diagnosis of endometritis was done by uterine lavage, and endometritis was considering cases of ≥5% neutrophils in each blade. The incidence of cytological endometritis in the herd was 22%, and did not differ between the categories analyzed (primiparous versus multiparous) (P>0.05), and the conception rate for first insemination was also similar between primiparous versus multiparous (P>0.05). However, the pregnancy rate at the end of BS was higher in multiparous cows (83.8%) when compared to primiparous (50.0%) cows (P<0.05). The presence or absence of cytological endometritis did not influence the conception rate (P>0.05) nor pregnancy rate at the end of the BS (P>0.05). Therefore, it can be concluded that the use of endometrial cytological cannot be justified as a diagnostic tool in Nelore beef cows.

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The aim of this study was to evaluate the antimicrobial activity in vitro of ethanolic extracts of Banisteriopsis anisandra. Tests were performed using the extracts overlay method in the culture medium for phytopathogenic fungi Rhizoctonia solani and Fusarium oxysporum, and disk diffusion for the microorganisms Staphylococcus aureus and Candida albicans. Ethanolic extracts from leaves were prepared by maceration (extract I) and decoction (extract II) at 430.0, 215.0 and 107.5 mg/mL. The growth inhibition of R. solani and F. oxysporum was determined by calculating the mycelia growth speed rate (MGSR) and, in relation C. albicans and S. aureus, it was determined by measuring the inhibition halos. Extracts that caused significant inhibition were also tested at 86.0, 64.5, 43.0 and 21.5 mg/mL for C. albicans and S. aureus. Both extracts showed inhibitory activity on the microorganisms studied. Rizoctonia solani showed lower MGSR in the presence of extract II (107.5 mg/mL) and Fusarium oxysporum showed slight MGSR reduction in the presence of extract I (107.5 mg/mL) and II (107.5 and 215 mg/mL). Ethanolic extracts I and II inhibited the growth of C. albicans, with the highest rates of inhibition observed in the presence of extract II (215.0 mg/mL). For S. aureus, the highest inhibitory activity was observed in the presence of ethanolic extract II, prepared by decoction at 430.0 mg/mL. Results showed a promising antimicrobial activity of extracts of B. anisandra, which may contribute to further studies leading to a future development of medicines to treat human and plant diseases caused by these organisms.

O objetivo deste estudo foi avaliar a atividade antimicrobiana in vitro de extratos etanólicos de Banisteriopsis anisandra. Os testes foram realizados utilizando o método de sobreposição de extratos em meio de cultura para fungos fitopatogênicos Rhizoctonia solani e Fusarium oxysporum e de difusão em disco para os microrganismos Staphylococcus aureus e Candida albicans. Foram testados de extratos etanólicos de folhas preparados por maceração (extrato I) e decocção (extrato II), nas concentrações de 430,0; 215,0 e 107,5 mg/mL. A inibição do crescimento de R. solani e F. oxysporum foi determinada pelo cálculo do índice de velocidade de crescimento micelial (IVCM) e de C. albicans e S. aureus, por meio da medida da halos de inibição. Os extratos que causaram inibição significativa também foram testados nas concentrações de 86,0; 64,5; 43,0 e 21,5 mg/mL para C. albicans e S. aureus. Ambos os extratos mostraram atividade inibitória sobre os microrganismos estudados. Rizoctonia solani apresentou menor IVCM na presença do extrato II (107,5 mg/mL) e Fusarium oxysporum apresentou discreta redução no IVCM na presença do extrato I (107,5 mg/mL) e II (107,5 e 215 mg/mL). Extratos etanólicos I e II inibiram o crescimento de C. albicans, com as maiores taxas de inibição observadas na presença do extrato II (215,0 mg/mL). Para S. aureus a maior atividade inibitória foi observada na presença do extrato II, na concentração de 430 mg/mL. Os resultados mostraram promissora atividade antimicrobiana de extratos de B. anisandra, o que pode contribuir para estudos futuros visando o desenvolvimento de medicamentos para doenças humanas e de plantas causadas por estes microrganismos.

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The aim was to investigate inter-tester and intra-tester reliability and parallel reliability between a visual assessment method and a method using a pachymeter for locating the mid-point of the patella in determining the medial/lateral patella orientation. Fifteen asymptomatic subjects were assessed and the mid-point of the patella was determined by both methods on two separate occasions two weeks apart. Inter-tester reliability was obtained by ANOVA and by intraclass correlation coefficient (ICC); intra-tester reliability was obtained by a paired t-test and ICC; and parallel reliability was obtained by Pearson's Correlation and ICC, for the measurement on the first and second evaluations. There was acceptable inter-tester agreement (p=0.490) and reliability for the visual inspection (ICC=0.747) and for the pachymeter (ICC=0.716) at the second evaluation. The inter-tester reliability in the first evaluation was unacceptable (visual ICC=0.604; pachymeter ICC=0.612). Although there was statistical similarity between measurements for the first and second evaluations for all testers, intra-tester reliability was not acceptable for both methods: visual (examiner 1 ICC=0.175; examiner 2 ICC=0.189; examiner 3 ICC=0.155) and pachymeter (examiner 1 ICC=0.214; examiner 2 ICC=0.246; examiner 3 ICC=0.069). Parallel reliability gave a perfect correlation at the first evaluation (r=0.828; p<0.001) and at the second (r=0.756; p<0.001) and reliability was between acceptable and very good (ICC=[0.748-0.813]). Both visual and pachymeter methods provide reliable and similar medial/lateral patella orientation and are reliable between different examiners, but the results between the two assessments at 2 weeks' interval demonstrated an unacceptable reliability.

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OBJECTIVE: To evaluate liver function and hemostatic parameters in postmenopausal women who have chronic infection with the hepatitis C virus and climacteric symptoms and are undergoing hormone therapy (HT) (standard dose of transdermal continuous combined hormone therapy). DESIGN: Fifty out of 336 postmenopausal patients with chronic infection with the hepatitis C virus were selected. The non-inclusion criteria were other chronic or systemic liver diseases, severe vascular diseases, autoimmune diseases or malignant tumors. The patients were randomized into two groups: the HT group with 25 patients to be given transdermal hormone therapy (50 microg estradiol plus 170 microg norethisterone/day) and the control group with the other 25 patients (no medication). Hepatic tests (alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase, total alkaline phosphatase, albumin, serum bilirubin) and hemostatic parameters (prothrombin time, factor V, fibrinogen) were evaluated at baseline and at 1, 4, 7 and 9 months of treatment. RESULTS: No significant changes in parameters were found in the comparison between the treated group and the controls, except for a decrease in total alkaline phosphatase (p = 0.002), presumably due to changes in bone remodelling. CONCLUSIONS: There were no changes in liver function after a 9-month treatment with transdermal estradiol plus norethisterone in symptomatic postmenopausal patients with hepatitis C.

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BACKGROUND: Results regarding the use of bovine somatotropin for enhancing fertility in dairy cattle are variable. Here, the hypothesis was tested that a single injection of a sustained-release preparation of bovine somatotropin (bST) during the preovulatory period would improve pregnancy success of lactating dairy cows at first service. RESULTS: The first experiment was conducted in a temperate region of Mexico. Cows inseminated following natural estrus or timed artificial insemination were given a single injection of bST or a placebo injection at insemination (n = 100 cows per group). There was no significant difference between bST and control groups in the proportion of inseminated cows diagnosed pregnant (29 vs 31% pregnant). The second experiment was performed during heat stress in Florida. Cows were subjected to an ovulation synchronization regimen for first insemination. Cows treated with bST received a single injection at 3 days before insemination. Controls received no additional treatment. As expected, bST did not increase vaginal temperature. Treatment with bST did not significantly increase the proportion of inseminated cows diagnosed pregnant although it was numerically greater for the bST group (24.2% vs 17.8%, 124-132 cows per group). There was a tendency (p = 0.10) for a smaller percent of control cows to have high plasma progesterone concentrations (>/= 1 ng/ml) at Day 7 after insemination than for bST-treated cows (72.6 vs 81.1%). When only cows that were successfully synchronized were considered, the magnitude of the absolute difference in the percentage of inseminated cows that were diagnosed pregnant between bST and control cows was reduced (24.8 vs 22.4% pregnant for bST and control). CONCLUSION: Results failed to indicate a beneficial effect of bST treatment on fertility of lactating dairy cows.

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The purpose of this study was to compare two lying and standing procedures for measuring orthostatic vital signs. Thirty-five normotensive participants (mean age 21.6 years)participated in a randomized crossover study. Measures of blood pressure (BP), heart rate, and dizziness were collected at different lying and standing times. AU subjects participated in a standardized walk paced at 4 miles per hour prior to lying. Using analysis of variance (ANOVA) with post hoc contrasts, the mean systolic BP differed between 5 and 10 minutes of lying (F = 21.33, p < .001) and the mean diastolic BP tended to differ between those time points (F = 5.23, p < .03). The mean standing systolic BP and dizziness rating were different between 0- and 2-minute intervals (F = 8.36, p < .01 and F = 7.15, p < .10). In normotensive participants following standardized exercise, orthostatic vital signs stabilized after lying 10 minutes.

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Host resistance to Trypanosoma cruzi infection is dependent on both natural and acquired immune responses. During the early acute phase of infection in mice, natural killer (NK) cell-derived IFN-gamma is involved in controlling intracellular parasite replication, mainly through the induction of nitric oxide biosynthesis by activated macrophages. We have shown that IL-12, a powerful inducer of IFN-gamma production by NK cells, is synthesized soon after trypomastigote-macrophage interaction. The role of IL-12 in the control of T. cruzi infection in vivo was determined by treating infected mice with anti-IL-12 monoclonal antibody (mAb) and analyzing both parasitemia and mortality during the acute phase of infection. The anti-IL-12 mAb-treated mice had higher levels of parasitemia and mortality compared to control mice. Also, treatment of infected mice with mAb specific for IFN-gamma or TNF-alpha inhibited the protective effect of exogenous IL-12. On the other hand, TGF-beta and IL-10 produced by infected macrophages inhibited the induction and effects of IL-12. Therefore, while IL-12, TNF-alpha and IFN-gamma correlate with resistance to T. cruzi infection, TGF-beta and IL-10 promote susceptibility. These results provide support for a role of innate immunity in the control of T. cruzi infection. In addition to its protective role, IL-12 may also be involved in the modulation of T. cruzi-induced myocarditis, since treatment of infected mice with IL-12 or anti-IL-12 mAb leads to an enhanced or decreased inflammatory infiltrate in the heart, respectively. Understanding the role of the cytokines produced during the acute phase of T. cruzi infection and their involvement in protection and pathogenesis would be essential to devise new vaccines or therapies.

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Host resistance to Trypanosoma cruzi infection in dependent on both natural and acquired immune responses. During the early acute phase of infection in mice, natural killer (NK) cell-derived IFN-gamma is involved in controlling intracellular parasite replication, mainly through the induction of nitric oxide biosynthesis by activate macrophages. We have shown that IL-12, a powerful inducer of IFN-gamma production by NK cells, is synthesized soon after trypomastigote-macrophage interaction. The role of IL-12 in the control of T. cruzi infection in vivo was determined by treating infected mice with anti-IL-12 monoclonal antibody (mAb) and analyzing both parasitemia and mortality during the acute phase of infection. The anti-IL-12 mAb-treated mice had higher levels of parasitemia and mortality compared to control mice. Also, treatment of infected mice with mAb spectific for IFN-gamma or TNF-alpha inhibited the protective effect of exogenous IL-12. On the other hand, TGF-beta and IL-10 produced by infected macrophages inhibited the induction and effects of IL-12. Therefore, while IL-12, TNF-alpha and IFN-gamma correlate with resistance to T. cruzi infection, TGF-beta and IL-10 promote susceptibility. These results provide support for a role of innate immunity in the control of T. cruzi infection. In addition to its protective role, IL-12 may also be involved in the modulation of T. cruzi-induced myocarditis, since treatment of infected mice with IL-12 or anti-IL-12 mAb leads to an enhanced or decreased inflammatory infiltrate in the heart, respectively. Understanding the role of the cytokine produced during the acute phase of T. cruzi infection and their involvement in protection and pathogenesis would be essential to devise new vaccines or therapies.

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Sycamore suspension cells (Acer pseudoplatanus L.) were grown in the presence of sublethal concentrations of copper (50 microM). During the first 5-6 days of treatment, growth was not affected, but cell respiration (coupled and uncoupled) declined to approximately 60% of its normal value. This decline of respiration was attributed to a progressive diminution of the number of mitochondria in copper-treated cells, based on the demonstration of the concomitant decline of (1) cardiolipin (diphosphatidylglycerol) and cytochrome aa3 (cytochrome oxidase), two specific markers of mitochondrial inner membrane, and (2) fumarase activity, a specific marker of mitochondrial matrix space. In addition, the mitochondria extracted from copper-treated cells presented the same properties as those from control cells, concerning substrate oxidation, cardiolipin and cytochrome aa3 contents, and fumarase activity. These results strongly suggest that copper triggered an arrest of mitochondrial biogenesis, which preceded cell division arrest.

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Methicillin-resistant Staphylococcus aureus (MRSA) isolates collected during a 7-month period in 1992 and 1993 at Hospital Pulido Valente (340 beds), Lisbon, Portugal, were characterized by a combination of genotypic and phenotypic methods. Clonal identities were determined by probing ClaI digests (i) with a mecA probe and (ii) with a Tn554 probe and (iii) by pulsed-field gel electrophoresis (PFGE) patterns of chromosomal SmaI digests. mecA-ClaI type I was predominant among these isolates (38 of 43). Most of these (37 of 38 [97.4%]) were associated with a single Tn554 pattern, pattern E, and the majority (23 of 38 [61%]) also showed a relatively uniform chromosomal background, as indicated by PFGE (PFGE pattern A). The major clone (mecA-ClaI type I::Tn554 type E and PFGE pattern A) at Hospital Pulido Valente was indistinguishable by these molecular typing criteria from the dominant clone that had been identified in two major current outbreaks of MRSA disease in Spain (Barcelona and Madrid). The Portuguese and Spanish clones also had a common heterogeneous class 3 phenotype and identical multidrug resistance patterns. The data presented in this work support the notion that MRSA clones can spread across considerable geographic distances.

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The dideoxynucleoside analogue 2',3'-dideoxyinosine (ddI) has been used in the clinic as an alternative drug to zidovudine (AZT) in the treatment of patients with the acquired immunodeficiency syndrome (AIDS). However, it shows significant and variable toxicity in patients. It is known that various dideoxynucleoside analogues can cause the termination of the DNA chain following incorporation of the corresponding triphosphate metabolite by the polymerases. In the case of ddI, the presumed active metabolite is 2',3'-dideoxyadenosine 5'-triphosphate (ddATP). In order to understand the molecular basis for the toxicity of ddI, we evaluated the relationship between the intracellular formation of ddATP, its incorporation into cellular DNA and the effects on the growth of U937 cells, a human monocytoid cell line. Dideoxyinosine was not significantly toxic to U937 cells at concentrations as high as 500 microM in a 72 hrs. growth inhibition assay. The results of the uptake of 3HddI in this cell line showed a proportional increase in total metabolites with increasing concentrations of the drug (1-20 microM) after a 24 hrs. exposure. Incubation with 10 microM 3HddI resulted in the formation of low levels of ddATP within a period of 2 hrs. A significant amount of ddI-derived radioactivity was found in both DNA and RNA after exposure to 10 microM 3HddI for 24 to 72 hrs. However, no evidence of incorporation of ddATP into the cellular DNA fraction was obtained in these experimental conditions. Therefore, the lack of significant toxicity of ddI to U937 cells can be explained, at least in part, by its inability to incorporate ddATP into its cellular DNA at the doses studied.

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Thymidine kinase is a key enzyme responsible for the activation of several anticancer and antiviral drugs. As the first enzyme in the salvage pathway of thymidine, it is regulated by the feedback inhibition exerted by the end-product of the pathway, namely thymidine 5'-triphosphate. 5'-Aminothymidine is a non-toxic analogue of thymidine capable of interfering with this regulatory mechanism. In fact, it has been shown that 5'-aminothymidine increases the cytotoxicity and metabolism of various thymidine analogues currently in use of the clinic as antineoplastic agents. This mini-review article focuses in the evidence supporting the role of 5'-aminothymidine as a potential prototype drug for a new class of anticancer agents: drugs which affect the regulation of key metabolic pathways that determine the efficacy of agents with cytotoxic activity. The mechanism of action, antineoplastic activities and basis for selectivity in tissue culture models are also described.

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