The efficacy of metformin as adjuvant to chemotherapy on IGF levels in non-diabetic female patients with progressive and non-progressive metastatic breast cancer.

OBJECTIVE: Some studies have shown that metformin inhibits the proliferation of breast cancer (BC) cells via multiple ways. One of these mechanisms is through the indirect control of the IGF-route mediated via the activation of the AMPK-LKB1 pathway in the liver, which leads to a decrease in blood glucose and insulin levels. The objective of this study was to investigate the effects of metformin as adjuvant to chemotherapy on IGF levels in female patients with progressive and non-progressive metastatic BC. PATIENTS AND METHODS: In this trial, 107 women receiving chemotherapy for metastatic breast cancer (MBC) were divided into two groups: the metformin group received 500 mg of metformin twice daily, whereas the control group did not receive any metformin. All patients received chemotherapy according to the South Egypt Cancer Institute's (SECI) established regimen. The level of IGF-1 was determined in the blood at the initiation of therapy (baseline) and at six months post treatment. RESULTS: No substantial differences were noted regarding IGF-1 levels in both groups at baseline (IGF-1 average level was 40.74 ± 36.16 vs. 32.06 ± 20.00 in the metformin and the placebo group, respectively, p = 0.462). While after six months, the mean IGF-1 level was 37.62 ± 31.35 vs. 39.12 ± 2 5.93 in the metformin and placebo groups, respectively, (p = 0.170). CONCLUSIONS: Metformin as an adjuvant to chemotherapy in MBC patients had no significant effect on reducing IGF-l levels which promotes the inhibition of the proliferation of BC cells in MBC patients.

Enhancement of Annexin V in response to combination of epigallocatechin gallate and quercetin as a potent arrest the cell cycle of colorectal cancer / Aumento da anexina V em resposta à combinação de galato de epigalocatequina e quercetina como uma potente parada do ciclo celular do câncer colorretal

Abstract Colorectal cancer (CRC) is one of the most common cancers leading to comorbidities and mortalities globally. The rational of current study was to evaluate the combined epigallocatechin gallate and quercetin as a potent antitumor agent as commentary agent for therapeutic protocol. The present study investigated the effect of epigallocatechin Gallate (EGCG) (150mg) and quercetin (200mg) at different proportions on proliferation and induction of apoptosis in human colon cancer cells (HCT-116). Cell growth, colonogenic, Annexin V in addition cell cycle were detected in response to phytomolecules. Data obtained showed that, the colony formation was inhibited significantly in CRC starting from the lowest concentration tested of 10 µg/mL resulting in no colonies as visualized by a phase-contrast microscope. Data showed a significant elevation in the annexin V at 100 µg/mL EGCG(25.85%) and 150 µg/mL quercetin (48.35%). Moreover, cell cycle analysis showed that this combination caused cell cycle arrest at the G1 phase at concentration of 100 µg/mL (72.7%) and 150 µg/mL (75.25%). The combined effect of epigallocatechin Gallate and quercetin exert antiproliferative activity against CRC, it is promising in alternative conventional chemotherapeutic agent.

Resumo O câncer colorretal (CCR) é um dos cânceres mais comuns, levando a comorbidades e mortalidade em todo o mundo. O racional do presente estudo foi avaliar a combinação de galato de epigalocatequina e quercetina como um agente antitumoral potente como agente de comentário para protocolo terapêutico. O presente estudo investigou o efeito de galato de epigalocatequina (EGCG) (150 mg) e quercetina (200 mg) em diferentes proporções na proliferação e indução de apoptose em células de câncer de cólon humano (HCT-116). O crescimento celular, colonogênico, anexina V, além do ciclo celular foram detectados em resposta a fitomoléculas. Os dados obtidos mostraram que a formação de colônias foi inibida significativamente no CRC a partir da concentração mais baixa testada de 10 µg/mL, resultando em nenhuma colônia conforme visualizado por um microscópio de contraste de fase. Os dados mostraram uma elevação significativa na anexina V a 100 µg/mL de EGCG (25,85%) e 150 µg/mL de quercetina (48,35%). Além disso, a análise do ciclo celular mostrou que essa combinação causou parada do ciclo celular na fase G1 na concentração de 100 µg/mL (72,7%) e 150 µg/mL (75,25%). O efeito combinado da epigalocatequina galato e quercetina exerce atividade antiproliferativa contra o CCR, é promissor como agente quimioterápico alternativo convencional.

Enhancement of Annexin V in response to combination of epigallocatechin gallate and quercetin as a potent arrest the cell cycle of colorectal cancer / Aumento da anexina V em resposta à combinação de galato de epigalocatequina e quercetina como uma potente parada do ciclo celular do câncer colorretal

Colorectal cancer (CRC) is one of the most common cancers leading to comorbidities and mortalities globally. The rational of current study was to evaluate the combined epigallocatechin gallate and quercetin as a potent antitumor agent as commentary agent for therapeutic protocol. The present study investigated the effect of epigallocatechin Gallate (EGCG) (150mg) and quercetin (200mg) at different proportions on proliferation and induction of apoptosis in human colon cancer cells (HCT-116). Cell growth, colonogenic, Annexin V in addition cell cycle were detected in response to phytomolecules. Data obtained showed that, the colony formation was inhibited significantly in CRC starting from the lowest concentration tested of 10 µg/mL resulting in no colonies as visualized by a phase-contrast microscope. Data showed a significant elevation in the annexin V at 100 µg/mL EGCG(25.85%) and 150 µg/mL quercetin (48.35%). Moreover, cell cycle analysis showed that this combination caused cell cycle arrest at the G1 phase at concentration of 100 µg/mL (72.7%) and 150 µg/mL (75.25%). The combined effect of epigallocatechin Gallate and quercetin exert antiproliferative activity against CRC, it is promising in alternative conventional chemotherapeutic agent.

O câncer colorretal (CCR) é um dos cânceres mais comuns, levando a comorbidades e mortalidade em todo o mundo. O racional do presente estudo foi avaliar a combinação de galato de epigalocatequina e quercetina como um agente antitumoral potente como agente de comentário para protocolo terapêutico. O presente estudo investigou o efeito de galato de epigalocatequina (EGCG) (150 mg) e quercetina (200 mg) em diferentes proporções na proliferação e indução de apoptose em células de câncer de cólon humano (HCT-116). O crescimento celular, colonogênico, anexina V, além do ciclo celular foram detectados em resposta a fitomoléculas. Os dados obtidos mostraram que a formação de colônias foi inibida significativamente no CRC a partir da concentração mais baixa testada de 10 µg/mL, resultando em nenhuma colônia conforme visualizado por um microscópio de contraste de fase. Os dados mostraram uma elevação significativa na anexina V a 100 µg/mL de EGCG (25,85%) e 150 µg/mL de quercetina (48,35%). Além disso, a análise do ciclo celular mostrou que essa combinação causou parada do ciclo celular na fase G1 na concentração de 100 µg/mL (72,7%) e 150 µg/mL (75,25%). O efeito combinado da epigalocatequina galato e quercetina exerce atividade antiproliferativa contra o CCR, é promissor como agente quimioterápico alternativo convencional.

Enhancement of Annexin V in response to combination of epigallocatechin gallate and quercetin as a potent arrest the cell cycle of colorectal cancer

Abstract Colorectal cancer (CRC) is one of the most common cancers leading to comorbidities and mortalities globally. The rational of current study was to evaluate the combined epigallocatechin gallate and quercetin as a potent antitumor agent as commentary agent for therapeutic protocol. The present study investigated the effect of epigallocatechin Gallate (EGCG) (150mg) and quercetin (200mg) at different proportions on proliferation and induction of apoptosis in human colon cancer cells (HCT-116). Cell growth, colonogenic, Annexin V in addition cell cycle were detected in response to phytomolecules. Data obtained showed that, the colony formation was inhibited significantly in CRC starting from the lowest concentration tested of 10 µg/mL resulting in no colonies as visualized by a phase-contrast microscope. Data showed a significant elevation in the annexin V at 100 µg/mL EGCG(25.85%) and 150 µg/mL quercetin (48.35%). Moreover, cell cycle analysis showed that this combination caused cell cycle arrest at the G1 phase at concentration of 100 µg/mL (72.7%) and 150 µg/mL (75.25%). The combined effect of epigallocatechin Gallate and quercetin exert antiproliferative activity against CRC, it is promising in alternative conventional chemotherapeutic agent.

Resumo O câncer colorretal (CCR) é um dos cânceres mais comuns, levando a comorbidades e mortalidade em todo o mundo. O racional do presente estudo foi avaliar a combinação de galato de epigalocatequina e quercetina como um agente antitumoral potente como agente de comentário para protocolo terapêutico. O presente estudo investigou o efeito de galato de epigalocatequina (EGCG) (150 mg) e quercetina (200 mg) em diferentes proporções na proliferação e indução de apoptose em células de câncer de cólon humano (HCT-116). O crescimento celular, colonogênico, anexina V, além do ciclo celular foram detectados em resposta a fitomoléculas. Os dados obtidos mostraram que a formação de colônias foi inibida significativamente no CRC a partir da concentração mais baixa testada de 10 µg/mL, resultando em nenhuma colônia conforme visualizado por um microscópio de contraste de fase. Os dados mostraram uma elevação significativa na anexina V a 100 µg/mL de EGCG (25,85%) e 150 µg/mL de quercetina (48,35%). Além disso, a análise do ciclo celular mostrou que essa combinação causou parada do ciclo celular na fase G1 na concentração de 100 µg/mL (72,7%) e 150 µg/mL (75,25%). O efeito combinado da epigalocatequina galato e quercetina exerce atividade antiproliferativa contra o CCR, é promissor como agente quimioterápico alternativo convencional.

Growth factors in relation to obesity, food habits, and microbiota among healthy Saudis: preliminary results.

OBJECTIVE: Obesity is a serious problem among Saudis because of the country's affluent lifestyle. Obesity is associated with various metabolic disorders and characterized by low-grade inflammation that leads to the release of pro-inflammatory cytokines, human growth factors (GFs), lipids, aberrant adipokines, and other chemokines from adipose tissue. The objective of this study is to delineate the effects of GFs on microbiota and their relationship to body mass index (BMI) and food habits. SUBJECTS AND METHODS: In a cross-sectional study, 32 randomly selected participants (16 males and 16 females) were enrolled in a survey covering their sociodemographic information, medical history, lifestyle, and dietary practices. The information on diet, health condition, food and drink intake habits were examined under four distinct BMI categories: normal, underweight, overweight, and obese. The participants' serum samples were analyzed for the various GFs using a human magnetic 30-plex panel multiplex assay. Bioinformatics analysis was performed to investigate which bacterial taxa are enriched and to predict the functional profiles of the samples. RESULTS: Correlational studies revealed sex-based differences between GFs and microbiota. Females exhibited a significant correlation between epidermal GF (EGF) and Proteobacteria, whereas males showed a significant correlation between fibroblast GF-basic and Actinobacteria. Interestingly, a combined analysis of both sexes showed a significant correlation between EGF and vascular endothelial GF with Firmicutes. The data in the underweight group revealed a correlation between granulocyte colony-stimulating factor (G-CSF) and hepatocyte GF with Firmicutes. In the obese group, a correlation was found between G-CSF and Actinobacteria. CONCLUSIONS: Our results identified links between GFs, microbiota, and BMI in a Saudi cohort. The insights from this preliminary study will contribute to the predictive diagnosis of obesity. However, further research involving a larger cohort will be necessary to understand the mechanistic aspects of these GFs to provide biomarkers of potential obesity.

Enhancement of Annexin V in response to combination of epigallocatechin gallate and quercetin as a potent arrest the cell cycle of colorectal cancer.

Colorectal cancer (CRC) is one of the most common cancers leading to comorbidities and mortalities globally. The rational of current study was to evaluate the combined epigallocatechin gallate and quercetin as a potent antitumor agent as commentary agent for therapeutic protocol. The present study investigated the effect of epigallocatechin Gallate (EGCG) (150mg) and quercetin (200mg) at different proportions on proliferation and induction of apoptosis in human colon cancer cells (HCT-116). Cell growth, colonogenic, Annexin V in addition cell cycle were detected in response to phytomolecules. Data obtained showed that, the colony formation was inhibited significantly in CRC starting from the lowest concentration tested of 10 µg/mL resulting in no colonies as visualized by a phase-contrast microscope. Data showed a significant elevation in the annexin V at 100 µg/mL EGCG(25.85%) and 150 µg/mL quercetin (48.35%). Moreover, cell cycle analysis showed that this combination caused cell cycle arrest at the G1 phase at concentration of 100 µg/mL (72.7%) and 150 µg/mL (75.25%). The combined effect of epigallocatechin Gallate and quercetin exert antiproliferative activity against CRC, it is promising in alternative conventional chemotherapeutic agent.

Control of eight predominant Eimeria spp. involved in economic coccidiosis of broiler chicken by a chemically characterized essential oil.

AIM: To control eight most predominant Eimeria spp. involved in the economic disease of coccidiosis in broiler chicken, by a chemically characterized essential oil of eucalyptus and peppermint. METHODS AND RESULTS: The experimental design consisted of 160 day-old-broiler chicks, divided into four equal groups (G1 , G2 , G3 and G4 ), with 40 birds per group. Each group was divided into four equal subgroups. Birds in G1 were deprived of essential oil treatment and of Eimeria challenge. Birds in G2 were unchallenged, and administered the essential oil in drinking water at 0.69 ml kg(-1) body weight. Birds in G3 were untreated with essential oil, and each of its four subgroups was challenged at a different age (14, 21, 28 and 35 days). Birds in G4 were treated with essential oil, and challenged in the same manner as for G3 . Equal number of birds from all subgroups (n = 10) were sacrificed at the sixth day after the time allocated for each challenge. The 6 day incubation period post challenge resulted in respective mean per cent weight increase in G2 and G1 birds equivalent to 57.8 and 53.1% (P < 0.05). In addition, the essential oil improved the per cent weight increase in challenged birds (54.6%) compared to the challenged-untreated birds (18.6%) (P < 0.05). The mean feed conversion, mortality, intestinal lesion scores and oocyst counts were significantly reduced in the challenged-treated birds compared to the challenged-untreated birds (P < 0.05). CONCLUSIONS: The results support the hypothesis of using the essential oils of eucalyptus and peppermint to control the most prevalent Eimeria spp. involved in coccidiosis of broiler chicken, helping in improvement of their production, alleviation of lesions and reduction in intestinal oocyst counts. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides information about the possibility of using this blend of essential oil as a coccidiostat for the protection of broiler chickens against the prevalent eight Eimeria spp. of coccidiosis.

Modulation by essential oil of vaccine response and production improvement in chicken challenged with velogenic Newcastle disease virus.

AIM: To evaluate the impact of Eucalyptus and peppermint essential oils on immune modulation and production of broiler chicken challenged with a molecularly characterized velogenic NewCastle disease virus (vNDV). METHODS AND RESULTS: The experimental design included five treatments with three replicate pens/treatment comprised of 12-day-old broilers chicks/replicate. The five treatments included a positive challenge control (non-NDV vaccinated/nonessential oil treated/challenged) (NNEOC), a negative challenge control (NDV vaccinated/essential oil treated/unchallenged) (VEOU), a non-NDV vaccinated/essential oil treated/challenged (NEOC), a NDV vaccinated/nonessential oil treated/challenged (VNEOC) and a NDV vaccinated/essential oil treated/challenged (VEOC). The lowest mean survival rate (0·0%) and lowest production performance were obtained by the positive challenge control, while the best mean survival (93·3%) and average body weight (2649 g) were obtained by the negative challenge controls (P < 0·05). Among the three others challenged treatments, the best mean survival (79·2%), highest mean body weight at 42 days of age (2445 g), the lowest feed conversion ratio (1·60) and the highest serum conversion immunopotentiation at 35 days of age determined by ELISA and hemagglutination titres were obtained by the VEOC birds compared with respective means obtained by birds of the NEOC and VNEOC treatments (P < 0·05). CONCLUSIONS: The results supported the possibility of using the essential oils of Eucalyptus and Peppermint in broilers to immunopotentiate the response to vaccination against velogenic NDV, helping in significant improvement of survival and production. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides information about the potential use of essential oils of eucalyptus and peppermint that can be exploited as commercial immunopotentiators for the protection of NDV-vaccinated broiler chickens against economic velogenic NDV.

Antimicrobial resistance of Staphylococcus species isolated from Lebanese dairy-based products.

The study evaluated the antimicrobial resistance of molecularly characterized strains of Staphylococcus aureus and S. saprophyticus isolated from 3 Lebanese dairy-based food products that are sometimes consumed raw: kishk, shanklish and baladi cheese. Suspected Staphylococcus isolates were identified initially using standard biochemical tests, then strains that were confirmed by polymerase chain reaction (29 S. aureus and 17 S. saprophyticus) were evaluated for their susceptibility to different antimicrobials. The highest levels of contamination with staphylococci were in baladi cheese. Resistance rates ranged from 67% to gentamicin to 94% to oxacillin and clindamycin. The results suggest that these locally made dairy-based foods may act as vehicles for the transmission of antimicrobial-resistant Staphylococcus spp.

Antimicrobial resistance of Staphylococcus species isolated from Lebanese dairy-based products

The study evaluated the antimicrobial resistance of molecularly characterized strains of Staphylococcus oureus and S. saprophyticus isolated from 3 Lebanese dairy-based food products that are sometimes consumed raw: kishk, shanklish and baladi cheese. Suspected Staphylococcus isolates were identified initially using standard biochemical tests, then strains that were confirmed by polymerase chain reaction [29 S, aureus and 17 S. saprophyticus] were evaluated for their susceptibility to different antimicrobials. The highest levels of contamination with staphylococci were in baladi cheese. Resistance rates ranged from 67% to gentamicin to 94% to oxacillin and clindamycin. The results suggest that these locally made dairy-based foods may act as vehicles for the transmission of antimicrobial-resistant Staphylococcus spp

Antimicrobial resistance and pathogenicity of Escherichia coli isolated from common dairy products in the Lebanon.

In a recent study, bacteria have been isolated from popular Lebanese dairy products, which had been collected in the Beqaa Valley, in north-eastern Lebanon. The foods investigated were two cheeses (shankleesh and baladi) and a dried fermented mixture of yogurt and wheat grains (kishk). Bacterial colonies on McConkey and sorbitol-McConkey agar that showed the morphology of Escherichia coli were biochemically tested and then classified, using PCR-based assays, into the various strains of pathogenic and non-pathogenic E. coli. Some of the confirmed E. coli isolates were proven to be pathogenic, including two identified as E. coli O157:H7. When the pathogenic isolates were tested for their susceptibility to 10 different antibiotics (all commonly used, by clinicians and veterinarians, for the treatment of infections with Gram-negative bacteria), each tested isolate was found to be highly resistant to at least one antibiotic. It therefore appears that, in Lebanon, some popular dairy products pose a public-health hazard, acting as vehicles for the transmission of drug-resistant pathogens.

Epigallocatechin-3-gallate induces apoptosis and cell cycle arrest in HTLV-1-positive and -negative leukemia cells.

The objective of this study is to evaluate the efficacy of epigallocatechin gallate against ATL cells. The anti-proliferative and pro-apoptotic effects of EGCG were evaluated in HTLV-1-positive and -negative cells. EGCG exhibited a marked decrease in proliferation of ATL cells at 96 h of treatment. The results indicated that TGF-alpha was down-regulated whereas levels of TGF-beta2 increased. Cell cycle distribution analysis revealed an increase in cells in the pre-G(1) phase which was confirmed by ELISA. The results on proteins showed an up-regulation of p53, Bax and p21 protein levels while the levels of Bcl-2alpha were down-regulated.

Mechanistic aspects of apoptosis induction by l-lysine in both HTLV-1-positive and -negative cell lines.

The retrovirus human T-cell lymphotrophic virus type-1 (HTLV-1) causes adult T-cell leukemia (ATL), which remains with no cure. This study evaluates the effects of l-lysine on proliferation and induction of apoptosis using non-cytotoxic concentrations of the test compound against HTLV-1 positive and negative malignant cell lines. The anti-proliferative effect of lysine was established and confirmed by studying the effects of the test compound on the expression of TGF mRNA expression by RT-PCR. To investigate the effect of l-lysine on the induction of apoptosis, DNA flow cytometry analyses was done and the results verified by cell death ELISA. The results indicated that a significant increase in the preG(1) phase and a decrease in the S phase of the cell cycle in all of the ATL cells tested. l-Lysine up-regulated p53, p21, and Bax protein levels and a down-regulation of Bcl-2alpha in all the cell lines tested. l-Lysine was found to exert its effect through the NF-kappaB pathway by inhibiting the p65 subunit specifically. Also l-lysine caused a decrease in the levels MMP-2 and MMP-9 as well as their enzymatic activity.

Apoptosis induction by Epican Forte in HTLV-1 positive and negative malignant T-cells.

The effects of a novel nutrient formulation Epican Forte (EF) were evaluated on proliferation and induction of apoptosis using non-cytotoxic concentrations against HTLV-1 positive (HuT-102 & C91-PL) and negative (CEM & Jurkat) cells. EF showed anti-proliferative effect as determined by MTT assay and TGF mRNA protein expression using RT-PCR. EF resulted in the down-regulation of TGF-alpha and an up-regulation in TGF-beta2. EF caused a significant increase in apoptotic cells in the preG1 phase. These results were confirmed using Cell Death ELISA and Annexin V-FITC. Induction of apoptosis was caused by an up-regulation of p53, p21 and Bax protein levels and a down-regulation of Bcl-2alpha protein expression level.

Determination of shelf life of concentrated yogurt (labneh) produced by in-bag straining of set yogurt using hazard analysis.

Strained yogurt, labneh, produced by straining cow's milk set yogurt in cloth bags, was stored at 5, 15, and 25 degrees C, and changes in microbial counts, pH, titratable acidity, percentage of free whey, and sensory attributes were monitored during storage. Counts of total aerobes, psychrotrophic yeasts, yeasts and molds, and lactic acid bacteria, except in samples stored at 25 degrees C, increased irrespective of storage temperature. The pH of samples decreased, titratable acidity and percentage of free whey increased, and texture defects were detected at a later stage than flavor changes during storage. Shelf-life data of labneh was adequately described by the Weibull distribution. The nominal shelf life determined using sensory changes and yeast counts as failure criteria ranged from 8.5 to 10.5, 4.7 to 5.8 and 2.3 to 2.7 d at 5, 15 and 25 degrees C, respectively. Q10 (shelf life at T degrees C/shelf life at T+10 degrees C) for flavor quality loss was 1.98 at 5 degrees C, and the corresponding activation energy was 11.3 kcal/mol.

NF-kappa B-independent suppression of HIV expression by ascorbic acid.

Ascorbic acid (ascorbate or vitamin C) has been shown to suppress the induction of HIV in latently infected T lymphocytic cells following stimulation with a tumor promoter (PMA) and inflammatory cytokine (TNF-alpha). To assess whether this inhibition was mediated via modulation of the cellular transcription factor, NF-kappa B, we carried out gel shift analysis on nuclear extracts prepared under different conditions of cell stimulation in the presence or absence of ascorbate, N-acetylcysteine (NAC), or zidovudine (AZT). Pretreatment of ACH-2 T cells by NAC followed by stimulation with PMA, TNF-alpha, or hydrogen peroxide (H2O2) resulted in strong suppression of NF-kappa B activation. In contrast, neither ascorbate nor AZT affected NF-kappa B activity under all three induction conditions in the ACH-2 cell line. Ascorbate and AZT also had no effect on NF-kappa B activation following TNF-alpha- or PMA-induced stimulation of U1 promonocytic cells. These results suggest that the molecular mechanism of HIV inhibition by ascorbate is not mediated via NF-kappa B inhibition, unlike that seen with other antioxidants.

Ascorbate effect on cytokine stimulation of HIV production.

We have recently shown that ascorbic acid (AA) suppresses the production of HIV in a latently infected T-lymphocytic cell line (ACH-2) following stimulation with the tumor promoter, PMA. To evaluate the effect of ascorbic acid on virus activation following treatment with inflammatory cytokine, we tested tumor necrosis factor alpha (TNF-alpha) whose levels are elevated in patients with HIV/AIDS. ACH-2 cultures, pretreated with various nontoxic concentrations of ascorbate or AZT were stimulated for 2 h with TNF-alpha, and incubated further with fresh supplements of ascorbate or AZT. At 24 to 48 h post-treatment, the RT activity released into culture supernatant was determined. Results showed that TNF-alpha alone caused approximately 13- to 16-fold stimulation in the level of extracellular RT. Pretreatment with ascorbic acid at 200 micrograms/ml caused a little more than about 2- to 4-fold reduction in extracellular RT levels. Most remarkably, exposure to 300 micrograms/ml ascorbate resulted in approximately 5- to 10-fold lowering of the extra-cellular RT titer. In contrast, no significant suppression in extracellular RT levels was seen with concentrations of AZT in the range of 1-5 micrograms/ml.