Biomedical subjects

C B Moore

Publications and source records attributed to C B Moore.

At least 19 recordsLinked to original sources

PubMed2006

Fungal contamination of bedding.

BACKGROUND: It is currently believed that most fungal exposure occurs external to the home. AIMS: To enumerate the fungal flora of used synthetic and feather pillows and the dust vacuumed from them, in the UK. METHODS: 10 pillows aged between 1.5 and >20 years in regular use were collected and quantitatively cultured for fungi. Swatches were taken from nine sections of the pillow and dust was also collected by vacuum from five pillows. Pillow vacuuming was carried out prior to pillow culture. All were cultured at room temperature, 30 and 37 degrees C for 7 days in broth before plating, and a subset were also cultured for 24 h in broth and then plated. Fungi were identified by standard morphological methods. RESULTS: The commonest three species isolated were Aspergillus fumigatus (n = 10), Aureobasidium pullulans (n = 6) and Rhodotorula mucilaginosa (n = 6). Another 47 species were isolated from pillows and vacuum dust. The number of species isolated per pillow varied from 4 to 16, with a higher number from synthetic pillows. Compared with the nonallergenic A. pullulans, more A. fumigatus was found in synthetic than feather pillows. CONCLUSIONS: We have examined pillows for fungal contamination, and show that the typical used pillow contains a substantial load of many species of fungi, particularly A. fumigatus. Given the time spent sleeping, and the proximity of the pillow to the airway, synthetic and feather pillows could be the primary source of fungi and fungal products. This has important implications for patients with respiratory disease, and especially asthma and sinusitis.

Allergens↗

PubMed2006

Comparison of two fluorescent whiteners, Calcofluor and Blankophor, for the detection of fungal elements in clinical specimens in the diagnostic laboratory.

Fluorescent whiteners, such as Blankophor and Calcofluor white, bind to chitin and cellulose, and fluoresce when exposed to UV light. Detection of fungal elements from skin and nail samples was faster and more accurate using Blankophor compared with potassium hydroxide preparations and Calcofluor (sensitivity and specificity 100% and 86% vs. 83-90% and 84-88%, or 80% and 84%, respectively). Visibility was improved, and the procedures were simple, inexpensive and rapid, all of which are important considerations in a busy diagnostic laboratory.

Benzenesulfonates↗

PubMed2005

Enhancement of cellular and humoral immunity following embryonic exposure to melatonin in turkeys (Meleagris gallopavo).

Two experiments were performed to determine the effect of in ovo melatonin supplementation on the ontogeny of immunity in the Large White turkey poult. Different levels of melatonin were injected into the air cell of the egg 4 days prior to hatch. In Experiment 1, turkey embryos received 3 ml of solution containing 200, 100, 50, 25, 10, or 1 microg/ml of melatonin. The hatchability at each dose was determined and compared to vehicle-injected controls. In Experiment 2, only poults from melatonin treatments in Experiment 1 that resulted in normal hatchability (10 and 1 microg/ml) were used. Lymphoproliferative responses to phytohemagglutinin (PHA-P) and primary antibody responses to Chukar red blood cells (CRBC) were determine at five time intervals: 0, 1, 7, 14, and 21 days post-hatch. At each of these times, including 28 days post-hatch, treatment effects on body weights were determined. At 28 days post-hatch, bursal, thymic, and splenic weights were obtained. In ovo melatonin administration significantly accelerated (P0.05) the development of cell-mediated (PHA-P) and humoral (CRBC) immune responses, and these responses were significantly elevated above vehicle-injected controls through 21 days post-hatch. No effect was observed on bursal, thymic, splenic or body weights. These data suggest that embryonic exposure to melatonin enhances post-hatch immune development and responsiveness.

Age Factors↗

PubMed2003

Correlation of statin-increased platelet APP ratios and reduced blood lipids in AD patients.

Platelets, like neurons, contain 120- to 130- and 110-kd amyloid precursor proteins (APPs). Their ratio is reduced in AD, further reductions correlating with reduced Mini-Mental Status Examination scores [r(11) = 0.69, p < 0.05]. As statins alter APP processing, platelet APPs were analyzed in patients with AD given anticholesterol drugs for 6 weeks. APP ratios increased [t(37) = -3.888, p = 0.0004], proportionally with reduced cholesterol [r(36) = -0.45, p = 0.005]. Longer trials may reveal slowed cognitive loss, validating this index.

Alzheimer Disease↗

PubMed2003

Melatonin enhances cellular and humoral immune responses in the Japanese quail (Coturnix coturnix japonica) via an opiatergic mechanism.

It is known that melatonin has important immunomodulatory properties in the Japanese quail. However, the mechanism of melatonin action on the immune system is not clearly understood in avian species. In mammals, the immunostimulatory properties of melatonin are mediated by the release of opioid peptides from activated T-lymphocytes. The present study was performed to determine if these same melatonin-induced opioids (MIO) are involved with the immunoenhancing effects of melatonin in quail. Three treatment groups were given melatonin (50 microg/ml) in the drinking water ad libitum along with naltrexone, a known opioid receptor-blocking agent. Melatonin was administered throughout the 3 week study and each bird received a daily intramuscular injection of naltrexone at a dose of 0.1, 1.0, or 10.0 mg/kg. In addition, three control groups were established that received only melatonin, naltrexone, or diluent. Evaluation of the cellular and humoral immune responses was initiated after 2 weeks of treatments. A cutaneous basophil hypersensitivity reaction to phytohemagglutinin (PHA-P) was measured to evaluate the cellular immune response. To evaluate the humoral immune response, primary antibody titers were determined 7 days post-intravenous injection with a Chukar red blood cell (CRBC) suspension. Both the cellular and humoral immune responses were significantly increased by 22 and 34%, respectively, upon melatonin exposure as compared to quail receiving diluent only. Concomitant administration of naltrexone and melatonin significantly reduced the immunoenhancing effect of melatonin across all naltrexone doses. We conclude that melatonin enhances a cellular and humoral immune response in Japanese quail via an opiatergic mechanism.

Adjuvants, Immunologic↗

PubMed2003

Multicenter evaluation of the reproducibility of the proposed antifungal susceptibility testing method for fermentative yeasts of the Antifungal Susceptibility Testing Subcommittee of the European Committee on Antimicrobial Susceptibility Testing (AFST-EUCAST).

OBJECTIVE: To evaluate the intra- and inter-laboratory reproducibility of a new standard for susceptibility testing of fermentative yeasts. This standard is based on the M27-A procedure of the National Committee for Clinical Laboratory Standards (NCCLS), but incorporates several modifications, including spectrophotometric growth-dependent endpoint reading. METHODS: Nine laboratories participated in the study. Common material lots were used to test six Candida species (one each of C. albicans, C. tropicalis, C. parapsilosis, C. glabrata, C. krusei, and C. lusitaniae), and two quality control strains (C. krusei ATCC6258 and C. parapsilosis ATCC22019). Triplicate testing on three separate days was performed in microtiter format with RPMI-2% glucose, pH 7.0. Flucytosine, fluconazole and itraconazole were tested. In total, 3888 MIC values were included in the analyses. Reproducibility was calculated by means of agreement (percentage of MICs within one two-fold dilution of the mode) and intraclass correlation coefficient (ICC, maximum value of 1). RESULTS: The average intra-laboratory agreements were 99% and 96% after 24 h and 48 h of incubation, respectively, with ICCs of 0.98 and 0.97 (P < 0.05). Two strains exhibiting a trailing effect showed intra-laboratory agreement of 92% and ICCs of < 0.91 at 48 h. The inter-laboratory agreement was 94% and 88% after 24 h and 48 h, respectively, with ICCs of 0.93 and 0.91 (P < 0.05). Lower values of agreement and ICCs were obtained for strains exhibiting trailing after 48 h of incubation. Itraconazole yielded the lowest values of reproducibility. CONCLUSION: The new procedure of EUCAST for antifungal susceptibility testing is a reproducible method within and between laboratories and offers several advantages over the NCCLS approved method.

Advisory Committees↗

PubMed2003

Immune function in turkey breeder hens during the short day prelighting period and renewal of photosensitivity for egg production.

Photorefractoriness (PR) in the turkey breeder hen is characterized by a lack of responsiveness to photoperiods that previously induced or maintained egg production. The consequence of PR is spontaneous regression of ovarian function and cessation of lay. Photosensitivity (PS) may be regained by giving at least 8 wk of short photoperiod (8L:16D) (light restriction). Following the transition from PR to PS, the birds may be photostimulated with long photoperiods, which allows for the recrudescence of ovarian function and normal egg production. Although the return of reproductive viability is the parameter for determining the successful recycle of ovarian function, there are no known reports of the physiological costs of this transition on immune function in the turkey breeder hen. We conducted an experiment to determine the immune responsiveness at various stages of recycle in the turkey breeder hen. Fifty photorefractory birds were selected and distributed equally among five treatment groups (time points). All birds were given an 8-wk period of light restriction (8L:16D) followed by a 12-wk period of photostimulation (16L:8D). The cellular (cutaneous basophil hypersensitivity CBH) and humoral (antibody titer) immune responses were determined in each treatment group (sequential time points): prelight restriction, 2-wk light restriction, 7-wk light restriction, 2-wk photostimulation, and 12-wk photostimulation. After 2-wk light restriction, there was a reduction in the cellular (64.1%) and humoral (59.5%) immune responses from that of the PR hens at the start. After 7-wk light restriction, the humoral responses increased (33.5%) as compared to the 2-wk light restriction time point Upon photostimulation, both the cellular (23.3%) and humoral (52.4%) immune responses were reduced at 2 wk of photostimulation as compared to the prior 7-wk light restriction time point. Finally, there was a rise in cellular (45.7%) and humoral (72.3%) immune responses after 12 wk of photostimulation as compared to the prior 2-wk photostimulation time point. We concluded that recycling of PR turkey hens was associated with altered cellular and humoral immune responses characterized by initial decline then recovery in both the light restriction and the postphotostimulation periods.

Animals↗

PubMed2002

Pineal melatonin secretion, but not ocular melatonin secretion, is sufficient to maintain normal immune responses in Japanese quail (Coturnix coturnix japonica).

Reports that plasma melatonin is an important immune regulator in avian species have been rather sparse and contradictory. Also, the primary source of immune-modulating melatonin has yet to be determined in birds. In Japanese quail (Coturnix coturnix japonica), the pineal gland and eyes contribute roughly two thirds and one third of the melatonin found in the blood, respectively. Two experiments were conducted to evaluate melatonin as an immune modulator in Japanese quail and to determine the primary source of immune-modulating melatonin in this species. Experiment 1 was designed to evaluate the involvement of the pineal gland and the eyes in immunocompetence. Each of three groups of quail was assigned a surgical treatment and the cellular and humoral immune responses were determined 8 weeks following surgery. The surgical treatments were pinealectomy (Px), sham pinealectomy (SH-Px), and ocular enucleation (eye removal (Ex)). Experiment 2 utilized exogenous melatonin as a replacement to reconstitute immune responses in surgically immunocompromised birds. In this experiment, 50.0 microg/ml of melatonin, or diluent only, was provided to Px and SH-Px birds in the drinking water ad libitum. The cellular and humoral immune responses were determined after 8 weeks of melatonin treatment. In both experiments, a cutaneous basophil hypersensitivity reaction to phytohemagglutinin was measured to evaluate the cellular immune response. To evaluate the humoral immune response, primary antibody titers were determined 7 days postintravenous injection with a Chukar red blood cell suspension. Flow cytometric analysis of peripheral blood lymphocytes was performed to determine the relative percentage of CD4(+) and CD8(+) T- and B-lymphocytes in all treatments of Experiment 2. In Experiment 1, both the SH-Px and Ex surgical treatments produced similar cellular and humoral immune responses, and these responses were significantly greater than those in Px-treated birds. Pinealectomy significantly reduced the cellular and humoral immune responses from SH-Px by 25.8% and 41.3%, respectively. In Experiment 2, Px again resulted in depressed cellular and humoral immune responses. In addition, Px significantly reduced CD8(+) T-lymphocyte numbers compared to SH-Px, while B-lymphocytes remained unchanged. Melatonin administration to Px birds increased the cellular (32.9%) and humoral (30.6%) immune responses to the level of control (SH-Px) birds, although this reconstitution was not due to increased CD8(+) T- or B-lymphocytes. From these data, it was clear that removal of the pineal gland, but not the eyes, reduced cellular and humoral immune responses, which were reconstituted to normal levels by exogenous melatonin. These data suggest that immunodepression is only observed in birds with two thirds of the plasma melatonin removed by pinealectomy. Removal of one third of the plasma melatonin (by ocular enucleation) is not sufficient to reduce cellular and humoral responses in the Japanese quail.

Animals↗

PubMed2002

Melatonin can produce immunoenhancement in Japanese quail (Coturnix coturnix japonica) without prior immunosuppression.

In recent years, it has been determined that melatonin has important immunostimulatory properties in mammalian and avian species. Typically, this immunoenhancement has only been examined in immunosuppressed animals. The effect of melatonin on normal (unsuppressed) immune systems is yet to be evaluated in avian species. An experiment was performed to determine if transient and/or continuous melatonin treatments could enhance immune functions in Japanese quail without prior immunosuppression. All quail were kept on a short photoperiod (8:16LD) throughout the study. In this experiment, 50.0 microg/ml melatonin was provided ad libitum to adult Japanese quail in the drinking water either continuously or for 3h per day. Control birds received diluent continuously throughout the experiment. Both the cellular and humoral immune responses were determined immediately after 3 weeks treatment. A cutaneous basophil hypersensitivity reaction to phytohemagglutinin (PHA-P) was measured to evaluate the cellular immune response. To evaluate the humoral immune response, primary antibody titers were calculated 7 days post-intravenous injection with a Chukar red blood cell (CRBC) suspension. The cellular and humoral immune responses were significantly elevated in the transient (3h) and continuous (24h) melatonin treatment groups as compared to the control group (0 h). As compared to the control group, the cellular immune response was increased 25% and 38% for the 3 and 24h melatonin treatments, respectively. The humoral immune response was increased 26% and 32% for the 3 and 24h melatonin treatments, respectively. Furthermore, continuous (24h) melatonin availability significantly increased the cellular, but not humoral immune responses as compared to the transient (3h) group, given melatonin for 3h prior to the scotophase (13:00-16:00 h). From these data, it was clear that transient and continuous administration of melatonin increased the cellular and humoral immune responses of Japanese quail without prior immunosuppression. These data suggest that the immunoenhancing effect of melatonin is not limited to reconstitution of weakened immune systems, but can be observed in normal, immunologically unsuppressed birds.

Adjuvants, Immunologic↗

PubMed2002

In vitro interaction of terbinafine with itraconazole, fluconazole, amphotericin B and 5-flucytosine against Aspergillus spp.

We investigated the in vitro interaction of terbinafine with itraconazole, fluconazole, amphotericin B and 5-flucytosine, against Aspergillus spp. We tested three isolates of Aspergillus fumigatus (one resistant to itraconazole), and two each of Aspergillus flavus, Aspergillus niger and Aspergillus terreus. We employed a broth microdilution-based method derived from an in vivo validated method capable of detecting itraconazole resistance in A. fumigatus. We studied the effect on the MICs by calculation of the fractional inhibitory concentration (FIC) and fractional fungicidal concentration (FFC) (99.99% kill). Itraconazole and terbinafine were synergic or additive in all strains (FIC = 0.15-1.0). Fluconazole and terbinafine were synergic with A. fumigatus, A. terreus and A. flavus (FIC = 0.3-0.5) and indifferent with A. niger (FIC = 2) isolates. Amphotericin B and terbinafine were mostly indifferent or antagonistic (FIC = 1.0-4.02). Flucytosine and terbinafine were usually indifferent or antagonistic (FIC = 0.63-8.5). FFCs were generally in accord with FICs. The use of terbinafine in combination therapy for Aspergillus infections with azoles seems promising, whereas terbinafine and amphotericin B or flucytosine in combination were less effective.

Amphotericin B↗

PubMed2002

Effect of melatonin supplementation on the ontogeny of immunity in the Large White turkey poult.

An experiment was performed to determine the effect of melatonin supplementation on the ontogeny of immunity in the Large White turkey poult. Melatonin (50 microg/mL) or diluent only (control) was administered via the drinking water from hatch to 28 d of age. The cutaneous basophil hypersensitivity (CBH) reaction to phytohemagglutinin (PHA-P) and primary antibody responses to Chukar red blood cells (CRBC) were determined at five intervals; 0, 1, 7, 14, and 21 d posthatch. At each of these times, including 28 d posthatch, 10 poults were killed and lymphoid organ and body weights were determined. Melatonin administration accelerated (P < or = 0.05) the development of cell-mediated (PHA-P-induced CBH reaction) and humoral (CRBC-induced antibody titer) immune responses, and these responses were elevated above controls through 21 d posthatch. The bursal weight, but not thymus or spleen, was elevated in melatonin treated poults as compared to controls. Body weights were increased in melatonin treated poults as compared to controls. These data suggest that posthatch melatonin supplementation is beneficial to neonatal immune parameters and growth responses of Large White turkey poults.

Aging↗

PubMed2001

Chronic hyperlactatemia in HIV-infected patients taking antiretroviral therapy.

OBJECTIVE: To determine the prevalence, course and risk factors for hyperlactatemia in HIV-infected patients. DESIGN: A prospective, longitudinal study of venous lactate concentrations over an 18-month period in 349 participants of the Western Australian HIV Cohort Study. RESULTS: In 516 patient-years of observation, two patients experienced severe fulminant lactic acidosis (lactate > 5 mmol/l) and hepatic steatosis attributable to nucleoside analogue reverse transcriptase inhibitors (NRTI). A further five patients with lesser elevations of lactate (2.8-4.1 mmol/l) but with symptoms of nausea or abdominal discomfort and evidence of hepatic steatosis had NRTI therapy revised, with relief of symptoms and a fall in lactate levels. Most remaining patients on highly active antiretroviral therapy (HAART) had mild, chronic, asymptomatic hyperlactatemia, with mean lactate level between 1.5 mmol/l and 3.5 mmol/l most commonly. Longitudinal data was analysed in a non-linear mixed effects growth model which indicated that average lactate levels rose after the start of HAART but tended to stabilise at low-grade elevation, with an average 0.23 mmol/l greater long term level in stavudine users compared with zidovudine users (p < 0.01). A multiple linear regression model showed that the association between stavudine and higher lactate level was not confounded by longer duration of total NRTI exposure. Risk of hyperlactatemia was not significantly associated with use of other NRTIs, protease inhibitors, non-nucleoside analogue reverse transcriptase inhibitors or multiple immunological and virological factors in multivariate analyses. CONCLUSIONS: Chronic, compensated, asymptomatic hyperlactatemia is common in patients taking HAART. Decompensated, life-threatening lactic acidosis/hepatic steatosis is rare. Treatment with stavudine appears to be the predominant risk factor for development of chronic hyperlactatemia.

Acidosis, Lactic↗

PubMed2001

In vitro activity of a new echinocandin, LY303366, and comparison with fluconazole, flucytosine and amphotericin B against Candida species.

OBJECTIVE: To investigate the in vitro activity of LY303366 (LY) against Candida isolates comprising nine different species and comparison with fluconazole (FLU), flucytosine (5FC) and amphotericin B (AMB). METHODS: The method used was a microtitre modification of the NCCLS M27-A accepted standard using either RPMI-1640 with 2% glucose (5FC and FLU) or antibiotic medium 3 with 2% glucose (LY and AMB). The minimum inhibitory concentration (MIC) was the lowest drug concentration that reduced growth by 80% compared with the drug-free control. Minimum fungicidal concentrations (MFCs; 99% kill) were also determined for all isolates for LY and AMB. RESULTS: Overall, 58 of 105 (55.2%) isolates were resistant to FLU (MIC < or = 16 mg/L). There was no relationship between FLU and LY MICs for C. albicans or non-albicans species. For all isolates, geometric mean (GM) MIC values and ranges (in mg/L) were: LY 0.011 and < or = 0.001-16, FLU 8.72 and < or = 0.125- > 128, 5FC 0.393 and < or = 0.03- > 32, AMB 0.046 and 0.008-0.125. Differences in susceptibility to LY were seen: C. parapsilosis (n = 12, GM 0.4 and range 0.125-16) and C. guilliermondii (n = 8, GM 0.46 and range 0.25-1) were both found to be significantly less susceptible to LY than all other species (P < or = 0.05). For all isolates, geometric mean MFC values and ranges (in mg/L) were: LY 0.032 and 0.002-16, AMB 0.143 and 0.03-2. The MFC value was the same as or only one drug dilution higher than the MIC value for 69.5% and 48.6% of isolates tested for LY and AMB, respectively. Tolerance was described in 13.3% and 5.7% of isolates for LY and AMB, respectively. A reproducibility study performed on 20% of the isolates showed that 90.5%, 100%, 95.2% and 100% of isolates retested were the same or within one well of the original MIC value for LY, FLU, 5FC and AMB, respectively. CONCLUSIONS: LY303366 shows promising antifungal activity in vitro and warrants further in vivo investigation.

Amphotericin B↗

PubMed2001

Susceptibility testing of Aspergillus flavus: inoculum dependence with itraconazole and lack of correlation between susceptibility to amphotericin B in vitro and outcome in vivo.

We have attempted to validate in Aspergillus flavus the main in vitro methodologies that have been used to detect resistance in Aspergillus fumigatus. We developed a murine model with two A. flavus isolates, one that was apparently resistant in vitro to amphotericin B (AFL5) and another that was resistant to itraconazole (AFL8). No correlation was found for amphotericin B in AFL5, since the in vivo response was compatible with a susceptible isolate. Modification of the in vitro susceptibility test methodology for amphotericin B was unsuccessful. Although AFL8 was apparently resistant to itraconazole in vitro, it was found to be susceptible in vivo. Additional in vitro work has detected weaknesses in the in vitro susceptibility methodology validated for A. fumigatus when applied to A. flavus. The principal problems are that changes in the inoculum have a large effect on the MICs of itraconazole for some A. flavus strains and that a trailing end point and spore sediment often appear when an inoculum with a higher colony count is used. We propose a modified method using a final inoculum of 2.5 x 10(4) CFU per ml of RPMI 1640 medium with 2% glucose buffered to pH 7.0 in a microtiter format, incubated for 48 h with no growth end point. Validation of this methodology requires one or more itraconazole-resistant A. flavus isolates, which have yet to be identified.

Amphotericin B↗

PubMed2001

In vitro activities of terbinafine against Aspergillus species in comparison with those of itraconazole and amphotericin B.

Compared with the in vitro activities of itraconazole (geometric mean MIC [GM], 0.56 microg/ml) and amphotericin B (GM, 0.66 microg/ml), the in vitro activity of terbinafine was inferior against Aspergillus fumigatus (GM, 19.03 microg/ml) (P < 0.05) and superior against A. flavus (GM, 0.10 microg/ml), A. terreus (GM, 0.16 microg/ml), and A. niger (GM, 0.19 microg/ml). Clinical correlation is required, as trailing endpoints are problematic.

Amphotericin B↗

PubMed2001

Antifungal susceptibility testing of fluconazole by flow cytometry correlates with clinical outcome.

Susceptibility testing of fungi by flow cytometry (also called fluorescence-activated cell sorting [FACS]) using vital staining with FUN-1 showed a good correlation with the standard M27-A procedure for assessing MICs. In this study we determined MICs for blood culture isolates from patients with candidemia by NCCLS M27-A and FACS methods and correlated the clinical outcome of these patients with in vitro antifungal resistance test results. A total of 24 patients with candidemia for whom one or more blood cultures were positive for a Candida sp. were included. Susceptibility testing was performed by NCCLS M27-A and FACS methods. The correlation of MICs (NCCLS M27-A and FACS) and clinical outcome was calculated. In 83% of the cases, the MICs of fluconazole determined by FACS were within 1 dilution of the MICs determined by the NCCLS M27-A method. For proposed susceptibility breakpoints, there was 100% agreement between the M27-A and FACS methods. In the FACS assay, a fluconazole MIC of <1 microg/ml was associated with cure (P < 0.001) whereas an MIC of > or =1 microg/ml was associated with death (P < 0.001). The M27-A-derived fluconazole MICs did not correlate with outcome (P = 1 and P = 0.133).

Adolescent↗

PubMed2000

Contribution of nucleoside analogue reverse transcriptase inhibitors to subcutaneous fat wasting in patients with HIV infection.

BACKGROUND: Progressive subcutaneous fat wasting, fat accumulation, dyslipidaemia and insulin resistance in HIV-infected patients on antiretroviral therapy has been attributed to the long-term toxicity of HIV protease inhibitors (PI). More recently, fat wasting has been observed in patients who have never taken a PI, implicating an independent effect of nucleoside analogue reverse transcriptase inhibitor (NRTI) therapy. OBJECTIVES: To determine the relative contribution of NRTI and PI, as well as any other factors, to fat wasting in HIV-infected patients. DESIGN: Longitudinal cohort study involving 277 participants of the Western Australian HIV Cohort Study. METHODS: The time to onset of clinically apparent fat wasting in patients receiving different antiretroviral regimens was compared using standardized clinical criteria. Regional fat measured by dual energy X-ray absorptiometry (DEXA) in 161 patients was also compared. The average rate of percentage fat reduction was estimated in 70 patients who had consecutive DEXA scans at approximately 6-monthly intervals. Multiple confounding factors were considered in the analyses. RESULTS: Progressive subcutaneous fat wasting, indistinguishable from that described in PI-treated patients, does occur in PI-naive, NRTI-treated patients. In patients taking triple combination antiretroviral therapy, age (relative risk = 1.052 per year; P < 0.0001), white race (relative risk = 3.9; P = 0.023), longer duration of dual NRTI therapy prior to addition of PI (relative risk = 1.021 per month; P = 0.0046) and increased cumulative time on stavudine-containing regimens compared with time on zidovudine-containing regimens (relative risk = 1.085 per month; P < 0.0001) are associated with increased risk of fat wasting. Stavudine increases the risk of fat wasting by 265% per year compared with zidovudine. However PI therapy is associated with faster progression to clinically apparent wasting compared with dual NRTI therapy without PI. The results of DEXA scanning supports these clinical data and suggest a non-linear decline in fat over time. CONCLUSIONS: NRTIs do have an independent contribution to fat wasting, but PI are the predominant influence and may act synergistically with NRTIs. NRTIs appear to predispose individuals to slowly progressive fat loss, which is markedly accelerated when a PI and NRTIs are combined. Of the NRTIs, stavudine leads to an earlier onset of clinically apparent fat wasting compared with zidovudine. Fat wasting associated with NRTI use may be a manifestation of mitochondrial toxicity, which may be exacerbated by PI use.

Absorptiometry, Photon↗

PubMed2000

Effects of lighting conditions and melatonin supplementation on the cellular and humoral immune responses in Japanese quail Coturnix coturnix japonica.

Two experiments were conducted to determine the effects of lighting conditions and melatonin supplementation on the cellular and humoral immune responses in Japanese quail. The first experiment was designed to evaluate differing light regimes as immune modulators in both adult and juvenile quail. The cellular and humoral immune responses were determined for three lighting conditions; short days (8:16LD), long days (16:8LD), and constant light (LL). In the second experiment, melatonin was administered in varying doses to adult quail placed in LL. The doses used in this experiment were 0.0, 0.5, 5.0, and 50.0 microg/ml melatonin given in the drinking water for 16 h per day for 2 weeks. The cellular and humoral immune responses were evaluated after 1 week of melatonin treatment. In both experiments, a cutaneous basophil hypersensitivity reaction to phytohemagglutinin (PHA-P) was measured to evaluate the cellular immune response. To evaluate the humoral immune response, primary antibody titers were calculated 7 days postintravenous injection with a Chukar red blood cell suspension. In the adult birds of experiment 1, both the 8:16LD and 16:8LD treatments produced similar cellular and humoral immune responses but these responses were significantly greater than those observed in LL. The juvenile birds held under 8:16LD also had significantly greater cellular and humoral immune responses as compared to juvenile birds held in LL. In experiment 2, there was a clear melatonin dose response on immune function in LL. The humoral immune response increased to a peak at the 5.0 microg/ml dose while the cellular immune response increased across all dose levels. From the present study it was clear that quail placed in daily light-dark cycles (LD), possessing a diurnal rhythm of melatonin, had significantly elevated immune responses as compared to those birds in LL. Furthermore, melatonin supplemented to birds exposed to LL was immuno-enhancing. This suggests that melatonin may be a mediator of the differences seen between LD and LL lighting conditions and may have important immune modulating properties.

Animals↗