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1.
Life Sci Space Res (Amst) ; 34: 37-44, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35940688

ABSTRACT

Future space missions will likely include plants to provide fresh foods and bioregenerative life support capabilities. Current spacecraft such as the International Space Station (ISS) operate at 1 atm (101 kPa) pressure, but future missions will likely use reduced pressures to minimize gas leakage and facilitate rapid egress (space walks). Plants for these missions must be able to tolerate and grow reliably at these reduced pressures. We grew two lettuce cultivars, 'Flandria' a green bibb-type and 'Outredgeous,' a red, loose-leaf type, under three pressures: 96 kPa (ambient control), 67 kPa (2/3 atm), and 33 kPa (1/3 atm) for 21 days in rockwool using recirculating nutrient film technique hydroponics. Each treatment was repeated three times using a different hypobaric chamber each time. A daily light integral of 17.2 Moles Photosynthetically Active Radiation per day was provided with metal halide lamps set to deliver 300 µmol m-2s -1 photosynthetic photon flux (PPF) for a 16 h photoperiod at 22 °C. Oxygen was maintained at 21 kPa (equal to 21% at 1 atm) and CO2 at 0.12 kPa (equal to 1200 ppm at 1 atm). Leaf area for 'Outredgeous' was reduced 20% and 38% at 67 kPa and 33 kPa respectively; shoot fresh mass was reduced 22% and 41% at 67 kPa and 33 kPa respectively when compared to control plants at 96 kPa. These trends were not statistically significant at P ≥ 0.05. Leaf area for 'Flandria' showed no difference between 96 and 67 kPa but was reduced 31% at 33 kPa; shoot fresh mass was reduced 6% and 27% at 66 kPa and 33 kPa respectively compared to 96 kPa. There were 10% and 25% increases in anthocyanin concentration at 66 kPa and 33 kPa compared to 96 kPa, potentially increasing the bioprotective capacity of the plant. Previous studies with other cultivars of lettuce showed slight change in growth across this range of pressures, suggesting responses may vary among genotypes, hypobaric exposure treatments, and / or environmental conditions. Collectively, the findings suggest further testing is needed to understand the effects of atmospheric pressure on plant growth.


Subject(s)
Environment, Controlled , Lactuca , Atmospheric Pressure , Carbon Dioxide , Photosynthesis , Plant Leaves
2.
Injury ; 50(12): 2158-2166, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31623902

ABSTRACT

BACKGROUND: Internal fixation remains the treatment of choice for non-displaced femoral neck fractures in elderly patients. Improved outcomes with arthroplasty following displaced femoral neck fractures may indicate that outcomes of non-displaced patterns should be reexamined. The aim of our study was to conduct a systematic review of the orthopaedic literature to determine the outcomes of internal fixation for the treatment of non-displaced and minimally displaced femoral neck fractures in elderly patients. METHODS: Relevant articles were identified using PubMed, Embase, and CENTRAL databases. Manuscripts were included if they contained (1) patients 60 years or older with (2) nondisplaced or minimally displaced (Garden I or II) femoral neck fractures (3) treated with internal fixation (4) separately reported outcomes in this patient population. The primary outcome was reoperation. Secondary outcomes included mortality, patient-reported outcomes, length of hospitalization, infection, and transfusions. Fixed and random effects modeling was used to determine pooled estimates of the outcomes. RESULTS: Twenty-seven studies were identified with a total of 21,155 patients, all of which were treated with internal fixation. The pooled risk of reoperation was 14.1% (95% CI: 10.6-18.2). The risk of one-year mortality was 14.6% (95% CI: 11.5-18.2) based on the reporting in 15 studies. CONCLUSIONS: The risk of reoperation and mortality following the treatment of nondisplaced femoral neck fractures in the elderly with internal fixation exceeds 14%. This complication profile may be unacceptably high. Arthroplasty may offer improved short-term functional outcomes and a reduced risk of reoperation. However, there is currently little evidence to consider this treatment to be an alternative to internal fixation.


Subject(s)
Femoral Neck Fractures/surgery , Fracture Fixation, Internal , Postoperative Complications/prevention & control , Aged , Arthroplasty/adverse effects , Arthroplasty/methods , Fracture Fixation, Internal/adverse effects , Fracture Fixation, Internal/methods , Humans , Risk Adjustment/methods
3.
Brain Res Cogn Brain Res ; 25(3): 624-31, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16216478

ABSTRACT

Locomotion and posture are influenced and controlled by vestibular, visual and somatosensory information. Optic flow and scene polarity are two characteristics of a visual scene that have been identified as being critical in how they affect perceived body orientation and self motion. The goal of this study was to determine the role of optic flow and visual scene polarity on adaptive modification in locomotor trajectory. An object is said to have visual polarity, or to be "visually polarized", when it contains an identifiable principal axis with one end distinct from the other. Two computer-generated virtual reality scenes were shown to subjects during 20 min of treadmill walking. One scene was a highly polarized scene, while the other was composed of objects displayed in a non-polarized fashion. Both virtual scenes depicted constant rate self motion equivalent to walking counterclockwise around the perimeter of a room. Subjects performed Stepping Tests blindfolded before and after scene exposure to assess adaptive changes in locomotor trajectory. Subjects showed a significant difference in heading direction, between pre- and post-adaptation Stepping Tests, when exposed to either scene during treadmill walking. However, there was no significant difference in the subjects' heading direction between the two visual scene polarity conditions. Therefore, it was inferred from these data that optic flow has a greater role than visual polarity in influencing adaptive locomotor function.


Subject(s)
Adaptation, Psychological/physiology , Locomotion/physiology , Visual Perception/physiology , Adult , Computer Graphics , Data Interpretation, Statistical , Female , Humans , Male , Postural Balance , Psychomotor Performance/physiology , Walking
4.
Exp Brain Res ; 166(2): 210-9, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16034569

ABSTRACT

The objective of this study was to investigate the adaptive effects of variation in the direction of optic flow, experienced during linear treadmill walking, on modifying locomotor trajectory. Subjects (n=30) walked on a motorized linear treadmill at 4.0 km h(-1) for 24 min while viewing the interior of a 3D virtual scene projected on to a screen 1.5 m in front of them. The virtual scene depicted constant self-motion equivalent to either (1) walking around the perimeter of a room to one's left (Rotating Room group) or (2) walking down the center of a hallway (Infinite Corridor group). The scene was static for the first 4 min and then constant rate self-motion was simulated for the remaining 20 min. Before and after the treadmill locomotion adaptation period subjects performed five stepping trials. In each trial they marched in place to the beat of a metronome at 90 steps min(-1) for a total of 100 steps while blindfolded in a quiet room. The subject's final heading direction (deg) and final X (fore-aft, cm) and final Y (medio-lateral, cm) positions were measured for each trial. During the treadmill locomotion adaptation period subjects' 3D torso position was measured. We found that subjects in the Rotating Room group, as compared with the Infinite Hallway group: (1) showed significantly greater deviation during post-exposure testing in the heading direction and Y position opposite to the direction of optic flow experienced during treadmill walking; and (2) showed a significant monotonically increasing torso yaw angular rotation bias in the direction of optic flow during the treadmill adaptation exposure period. Subjects in both groups showed greater forward translation (in the +X direction) during the post-treadmill stepping task that differed significantly from their pre-exposure performance. Subjects in both groups reported no perceptual deviation in position during the stepping tasks. We infer that viewing simulated rotary self-motion during treadmill locomotion causes adaptive modification of sensorimotor integration in the control of position and trajectory during locomotion, which functionally reflects adaptive changes in the integration of visual, vestibular, and proprioceptive cues. Such an adaptation in the control of position and heading direction during locomotion, because of the congruence of sensory information, demonstrates the potential for adaptive transfer between sensorimotor systems and suggests a common neural site for processing and self-motion perception and concurrent adaptation in motor output.


Subject(s)
Adaptation, Physiological/physiology , Motion Perception/physiology , Psychomotor Performance/physiology , User-Computer Interface , Walking/physiology , Adult , Biomechanical Phenomena , Humans , Photic Stimulation , Posture/physiology , Rotation
5.
Clin Lab Haematol ; 20(4): 207-11, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9777265

ABSTRACT

The objective of this study was to determine the frequency of ethnic groups within the antenatal population in central Manchester and thereby ensure that the haemoglobinopathy service was targeting the correct population and their needs. Ethnic data collection records of 6718 patients were analysed over a 7 month period. Of these 62.3% stated that they were White, 13.2% Asian, 7.9% Black, 3.8% Chinese or 'other ethnic groups' and 12.7% gave no information about their ethnic background. A subset of 1144 patients were screened for haemoglobinopathies over a 1 month period. The incidence of haemoglobinopathies within the screened population was 2.62%, and comprised 0.69% beta thalassaemia trait, 1.22% sickle cell trait, 0.43% haemoglobin C trait and 0.26% haemoglobin D trait. The total incidence of haemoglobinopathies was highest within the Black population (18.2%), followed by the no information group (5.6%), Asian (3.35%) and white (0.26%). The high proportion of ethnic minorities and the significant carrier frequency in the no information group, support our view that non-selective screening should be offered to the antenatal population of central Manchester.


Subject(s)
Hemoglobinopathies/diagnosis , Hemoglobinopathies/ethnology , Mass Screening , Prenatal Diagnosis , England/epidemiology , Female , Gene Frequency , Hemoglobinopathies/blood , Hemoglobins/analysis , Heterozygote , Humans , Incidence , Pilot Projects , Pregnancy , Retrospective Studies
6.
Clin Lab Haematol ; 20(1): 31-40, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9681208

ABSTRACT

The Bio-Rad Variant Haemoglobin Testing System is an automated analyser which uses the principle of cation exchange high performance liquid chromatography. This evaluation was undertaken to examine the effectiveness of the instrument as a screening mechanism to assist in the diagnosis of haemoglobinopathies. The ability to quantify haemoglobins A2 and F and to 'flag' other haemoglobin variants was tested. Within-batch precision was excellent and between-batch precision was good. Linearity and sensitivity compared favourably with the manufacturer's published ranges. The level of carry-over for haemoglobins F, S and A was less than 0.25%. The mean carry-over for haemoglobin A2 was 2.08%. This higher figure reflected the smaller absolute difference between the high and low samples for this parameter. The instrument never failed to indicate the presence of an abnormal haemoglobin in 271 selected samples. The instrument was reliable throughout the evaluation and at no time was a run aborted.


Subject(s)
Chromatography, High Pressure Liquid/instrumentation , Chromatography, High Pressure Liquid/methods , Hemoglobinopathies/blood , Hemoglobinopathies/diagnosis , Hemoglobins/analysis , Cations , Chromatography, Ion Exchange/methods , Drug Stability , Evaluation Studies as Topic , Hemoglobinopathies/prevention & control , Humans , Linear Models , Mass Screening/methods , Reference Values , Reproducibility of Results , Sensitivity and Specificity , Specimen Handling
7.
Anaesthesia ; 53(3): 296-8, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9613276

ABSTRACT

The effect of pre- versus postincisional epidural blockade without the use of systemic opioids was investigated in a randomised, double-blind study of two groups of 25 patients undergoing abdominal hysterectomy performed under general anaesthesia. The first group received, via a lumbar epidural catheter, 0.9% saline (16 ml) 15 min prior to surgical incision and 0.5% bupivacaine (15 ml) and fentanyl 50 micrograms (1 ml) 15 min prior to skin closure. The second group of 25 patients received the same amount of bupivacaine and fentanyl 15 min pre-incision and saline prior to skin closure. Visual analogue pain scores and patient-controlled morphine consumption were measured at specified times for 48 h. We were unable to detect any significant difference in either of the outcome measures of the two groups and thus were unable to demonstrate that epidural blockade using local anaesthetic and opioid has a pre-emptive effect.


Subject(s)
Anesthesia, Epidural/methods , Hysterectomy , Pain, Postoperative/prevention & control , Adult , Analgesia, Patient-Controlled , Analgesics, Opioid/administration & dosage , Anesthetics, Local/administration & dosage , Blood Pressure/drug effects , Bupivacaine/administration & dosage , Double-Blind Method , Drug Administration Schedule , Drug Combinations , Female , Fentanyl/administration & dosage , Humans , Morphine/administration & dosage
8.
Biochem Pharmacol ; 53(8): 1115-21, 1997 Apr 25.
Article in English | MEDLINE | ID: mdl-9175716

ABSTRACT

Two versions of the comet assay have been used to identify the difference in the modes of action of AZQ (2,5-diaziridinyl-3,6-bis(carboethoxyamino)-1,4-benzoquinone) and BZQ (2,5-diaziridinyl-3,6-bis(ethanolamino)-1,4-benzoquinone) in human leukaemia K562 cells and a K562-derived resistant cell line, BZQR. Using the standard alkaline assay, AZQ produced dose-dependent changes in the mean comet moments from K562 cells, consistent with the formation of strand breaks. This damage was repaired over a period of 6 hr after removal of the drug. The resistant cell line, BZQR, showed much smaller changes in comet moment under identical conditions. In contrast to AZQ, BZQ did not produce any measurable strand breaks in the K562 or BZQR cells. However, the comet radiation/crosslinking assay and a fluorescence-based assay revealed that BZQ extensively cross-links DNA in K562 cells. The extent of cross-linking is greatly reduced in the resistant cell line.


Subject(s)
Antineoplastic Agents/pharmacology , Aziridines/pharmacology , Benzoquinones/pharmacology , DNA Damage , Cross-Linking Reagents/pharmacology , DNA Repair , Drug Resistance , Electrophoresis, Agar Gel/methods , Humans , Tumor Cells, Cultured
9.
Anaesthesia ; 49(5): 450-1, 1994 May.
Article in English | MEDLINE | ID: mdl-8210000
10.
Clin Chim Acta ; 203(2-3): 285-94, 1991 Dec 16.
Article in English | MEDLINE | ID: mdl-1777988

ABSTRACT

Serum alkaline phosphatase, alkaline phosphatase isoenzymes, and urinary hydroxyproline excretion were studied in 20 young adult sickle cell patients and 58 matching normal controls. Total alkaline phosphatase was significantly higher in the sickle cell patients than in controls. Heat inactivation test and isoenzyme electrophoresis indicated that bone is the predominant isoenzyme in patients. Hydroxyproline excretion was significantly higher in the sickle cell patients than in controls. Serum total alkaline phosphatase correlated well with urinary hydroxyproline excretion in sickle cell patients (r = 0.73). Both alkaline phosphatase and hydroxyproline increased with age in the sickle cell patients. This study suggests that delayed growth and/or bone destruction may contribute to the elevated levels of alkaline phosphatase and urinary hydroxyproline.


Subject(s)
Alkaline Phosphatase/blood , Anemia, Sickle Cell/metabolism , Hydroxyproline/urine , Isoenzymes/blood , Adolescent , Adult , Aging/metabolism , Female , Humans , Male , Saudi Arabia
11.
J Clin Pathol ; 42(12): 1302-8, 1989 Dec.
Article in English | MEDLINE | ID: mdl-2613925

ABSTRACT

A modified, small volume, two phase, disc culture system for CFU-GM (seven and 14 days of incubation) was compared with a standard single layer system. The 1 ml single layer cultures were counted unstained in situ before both sets of cultures were transferred to glass slides for staining. Bone marrows were cultured from forty eight subjects, including normal controls and patients with acute non-lymphoblastic leukaemia, acute lymphoblastic leukaemia, and myelodysplastic syndrome. Observer error was least with the disc cultures, whereas variation between replicate cultures was similar for both methods. A high degree of correlation was found between the two methods for both day 7 (r = 0.90) and day 14 (r = 0.91) cultures. The number of colonies and clusters was higher with the disc system, indicating better cloning efficiency. Analysis of subsets of clinical groups showed similar patterns of abnormality with both systems. The simplicity of the method makes the use of this technology possible in most laboratories, and the superior morphological resolution may increase the clinical usefulness of such studies.


Subject(s)
Bone Marrow/pathology , Colony-Forming Units Assay/methods , Granulocytes/pathology , Humans , Leukemia, Myeloid, Acute/pathology , Macrophages/pathology , Myelodysplastic Syndromes/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Time Factors
12.
Antiviral Res ; 6(4): 189-95, 1986 Jul.
Article in English | MEDLINE | ID: mdl-2427021

ABSTRACT

Intranasal inoculation of weanling mice with herpes simplex virus type 2 (HSV-2) provides an experimental infection that closely resembles disseminated and central nervous system HSV infections of human neonates. Intraperitoneal treatment with acyclovir (ACV) successfully reduced mortality even when therapy was begun as late as 2 days and oral therapy as late as 4 days after viral challenge. Treatment with ACV beginning on day 1 completely inhibited HSV-2 replication in lung, spleen, kidney, olfactory lobe, and cerebrum and decreased viral titers in the pons by 2-3 logs. Comparison of these data with our previous experiments using adenine arabinoside and adenine arabinoside 5' monophosphate indicates that ACV is more effective in the murine model of neonatal disease and suggests that ACV may also be more effective in treating the disease in humans.


Subject(s)
Acyclovir/therapeutic use , Herpes Simplex/drug therapy , Acyclovir/administration & dosage , Administration, Oral , Animals , Brain/microbiology , Female , Humans , Infant, Newborn , Injections, Intravenous , Kidney/microbiology , Lung/microbiology , Mice , Olfactory Bulb/microbiology , Pons/microbiology , Simplexvirus/growth & development , Spleen/microbiology , Vidarabine/therapeutic use , Vidarabine Phosphate/therapeutic use
13.
Antiviral Res ; 5(5): 281-90, 1985 Oct.
Article in English | MEDLINE | ID: mdl-2998276

ABSTRACT

The effect of topical treatment with butylated hydroxytoluene (BHT) was evaluated in primary and recurrent genital herpes simplex virus type 2 (HSV-2) infection of guinea pigs. In the first experiment, treatment with placebo, 5%, 10%, or 15% BHT was initiated 48 h after viral inoculation and continued 4 times daily for 15 days. During primary infection no differences in maximum lesion severity or titers of virus in lesions were observed, however, lesion duration was reduced in BHT-treated animals resulting in a significantly smaller lesion score-day area under the curve. In a second experiment using U.S.P. mineral oil as an additional placebo, BHT placebo and 15% BHT in a double blind trial, similar results were obtained. Treatment of the recurrent infection in either experiment failed to alter the number of recurrent episodes or days with lesions.


Subject(s)
Butylated Hydroxytoluene/therapeutic use , Herpes Genitalis/drug therapy , Administration, Topical , Animals , Butylated Hydroxytoluene/administration & dosage , Butylated Hydroxytoluene/toxicity , Disease Models, Animal , Drug Evaluation, Preclinical , Female , Guinea Pigs , Simplexvirus/drug effects
15.
Intervirology ; 24(4): 226-31, 1985.
Article in English | MEDLINE | ID: mdl-3000982

ABSTRACT

After recovery from initial genital herpes simplex virus (HSV) infections, female guinea pigs developed spontaneous recurrent infections characterized by discrete erythematous or vesicular herpetic lesions on the external genital skin. HSV type 2 (HSV2) caused significantly more recurrent infections in guinea pigs than did HSV type 1 (HSV1). HSV2-infected animals demonstrated a significant decline in frequency of recurrences over time. The viral nature of the recurrent lesions was confirmed by recovery of infectious HSV, detection of HSV antigen, and histologic examination. Latent HSV2 could be demonstrated in dorsal root ganglia and external genital skin after recovery from the primary infection. Recurrent genital HSV infection in the guinea pig shares many features with recurrent genital herpes in humans and provides a model for studying the relationship between latency and recurrences and for exploring methods for control of recurrent disease.


Subject(s)
Disease Models, Animal , Herpes Genitalis , Animals , Antigens, Viral/immunology , Female , Ganglia, Spinal/immunology , Ganglia, Spinal/microbiology , Ganglia, Spinal/pathology , Guinea Pigs , Herpes Genitalis/immunology , Herpes Genitalis/microbiology , Herpes Genitalis/pathology , Recurrence , Simplexvirus/immunology , Simplexvirus/isolation & purification , Skin/immunology , Skin/microbiology , Skin/pathology
16.
Antiviral Res ; 3(4): 253-67, 1983 Nov.
Article in English | MEDLINE | ID: mdl-6320718

ABSTRACT

Intravaginal inoculation of mice with herpes simplex virus (HSV) provides a model infection of genital herpes to determine the effectiveness of potential antiviral agents. topical (intravaginal) treatment with 1% or 5% acyclovir (ACV) in an ointment of gel vehicle initiated 3, 6 or 24 h after inoculation with HSV type 2, significantly inhibited viral replication in the genital tract and usually reduced final mortality. Treatment with 5% ACV initiated 48 or 72 h after infection also reduced vaginal virus titers but did not alter final mortality. When mice were inoculated with HSV type 1 treatment with 5% ACV significantly reduced viral replication in the genital tract when begun as late as 72 h. In HSV-2 infected mice, treatment initiated 3 h but not 24 h after infection prevented the establishment of latent infection in sacral ganglie. These results suggest that topical ACV may be effective antiviral agent for primary genital herpes in humans.


Subject(s)
Acyclovir/therapeutic use , Herpes Genitalis/drug therapy , Acyclovir/administration & dosage , Administration, Topical , Animals , Female , Male , Mice , Simplexvirus/drug effects , Vagina/microbiology
17.
J Infect Dis ; 146(3): 397-404, 1982 Sep.
Article in English | MEDLINE | ID: mdl-6286797

ABSTRACT

Guinea pigs inoculated intravaginally with herpes simplex virus type 2 (HSV-2) developed a self-limiting infection characterized by vesiculo-ulcerative lesions on the external genital skin, urinary retention, and hindlimb paralysis. Infection rarely resulted in death. Virologic, histologic, and immunoperoxidase data suggested the following scheme for viral pathogenesis: initial replication in the introitus, vagina, and bladder; spread via sensory nerves to the lumbosacral dorsal root ganglia and spinal cord, and transmission via peripheral nerves to the external genital skin to produce the characteristic lesions. After recovery from primary infection, animals developed recurrent vesicular lesions, shed virus from genital sites in the absence of lesions, and harbored latent HSV-2 in dorsal root ganglia. Genital infection in the guinea pig shares many features with genital herpes in humans and provides a model to explore mechanisms of latency and reactivation and to evaluate several methods for control of recurrent disease.


Subject(s)
Herpes Genitalis/microbiology , Simplexvirus/growth & development , Animals , Brain/microbiology , Disease Models, Animal , Female , Ganglia, Spinal/microbiology , Guinea Pigs , Male , Nervous System/microbiology , Recurrence , Skin/microbiology , Skin/pathology , Spinal Cord/microbiology , Time Factors , Urinary Bladder/microbiology , Uterus/microbiology , Vagina/microbiology
18.
Am J Med ; 73(1A): 125-31, 1982 Jul 20.
Article in English | MEDLINE | ID: mdl-7102699

ABSTRACT

The effect of oral or intraperitoneal administration of acyclovir was evaluated in four experimental models of herpes simplex virus (HSV) encephalitis in mice. Mice were inoculated with HSV-1 or HSV-2 intracerebrally or with HSV-2 intranasally, intraperitoneally, or intravaginally. With all four routes of inoculation, oral acyclovir therapy significantly reduced mortality when started as late as 72 to 96 hours after viral challenge. Intraperitoneal acyclovir was not effective in protecting mice inoculated intravaginally, but was effective if given 24 to 48 hours after intracerebral or intranasal challenge and as late as 96 hours after intraperitoneal infection. Oral acyclovir was more active than intraperitoneal treatment in all four model infections. Levels of acyclovir inhibitory for HSV in cell culture were maintained in plasma and brain tissue throughout oral treatment but lasted only three to six hours after each intraperitoneal treatment. These results suggest that acyclovir may be useful in treating serious HSV infections in humans.


Subject(s)
Antiviral Agents/administration & dosage , Encephalitis/drug therapy , Guanine/analogs & derivatives , Herpes Simplex/drug therapy , Acyclovir , Administration, Oral , Animals , Antiviral Agents/metabolism , Brain/metabolism , Female , Guanine/administration & dosage , Guanine/metabolism , Injections, Intraperitoneal , Mice , Time Factors , Tissue Distribution
19.
Am J Med ; 73(1A): 132-7, 1982 Jul 20.
Article in English | MEDLINE | ID: mdl-6285702

ABSTRACT

Murine cytomegalovirus (MCMV) is inhibited in vitro by 1 to 2 microM acyclovir. Therapy of a systemic MCMV infection in weanling mice with acyclovir was only minimally effective when drug was administered intraperitoneally, while oral administration by addition of acyclovir to the drinking water was highly efficacious in mice with disseminated MCMV. Effective therapy was characterized by reduction of virus titers in lung, liver, spleen, and kidney. In mice chronically infected with MCMV, treatment for 30 days with oral acyclovir eliminated or reduced virus titers in all target organs except the salivary gland. Therapeutic efficacy in this model infection using oral administration of acyclovir could be correlated with the achievement of acyclovir levels in the plasma of experimental animals two to 10 times greater than the mean inhibitory concentration for MCMV in vitro throughout treatment. The lack of efficacy observed when drug was administered intraperitoneally was associated with acyclovir levels exceeding 1 microM for one to three hours after each dose.


Subject(s)
Antiviral Agents/therapeutic use , Cytomegalovirus Infections/drug therapy , Cytomegalovirus/drug effects , Guanine/analogs & derivatives , Acute Disease , Acyclovir , Administration, Oral , Animals , Antiviral Agents/blood , Chronic Disease , Female , Guanine/blood , Guanine/therapeutic use , Mice
20.
Biochim Biophys Acta ; 705(2): 257-63, 1982 Jul 26.
Article in English | MEDLINE | ID: mdl-6810939

ABSTRACT

The kinetics of the ultrafast ligand recombination following 347 nm laser photolysis of aqueous solutions of carbonmonoxyhaemogloblin have been investigated. The process is biphasic and the rate constants for the two processes as functions of temperature have been used to give activation energies of 6 +/- 3.9 kJ . mol-1 for the fast process and 31 +/- 4.8 kJ . mol-1 for the slow process. Frequency factors have also been calculated. The two processes are discussed in relation to both low-temperature studies and model calculations on the rate of entry of carbon monoxide into haem proteins.


Subject(s)
Carboxyhemoglobin/metabolism , Hemoglobins/metabolism , Lasers , Photolysis , Carbon Dioxide/metabolism , Cold Temperature , Humans , Kinetics , Models, Biological , Thermodynamics
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