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PubMed2004

Compartmentalization of prion isoforms within the reproductive tract of the ram.

Cellular prion protein (Prp(C)) is a glycoprotein usually associated with membranes via its glycosylphosphatidylinositol (GPI) anchor. The trans-conformational form of this protein (Prp(SC)) is the suggested agent responsible for transmissible neurodegenerative spongiform encephalopathies. This protein has been shown on sperm and in the reproductive fluids of males. Antibodies directed against the C-terminal sequence near the GPI-anchor site, an N-terminal sequence, and against the whole protein showed that the Prp isoforms were compartmentalized within the reproductive tract of the ram. Immunoblotting with the three antibodies showed that the complete protein and both N- and C-terminally truncated and glycosylated isoforms are present within cauda epididymal fluid and seminal plasma. Moreover, we demonstrate that in these fluids, the Prp(C) isoforms are both in a soluble state as well as associated with small membranous vesicles (epididymosomes). We also report that only one major glycosylated 25 kDa C-terminally truncated Prp(C) isoform is associated with sperm from the testis, cauda epididymis, and semen, and this form is also present in the sperm cytoplasmic droplets that are released during maturation. In sperm, this C-terminal truncated form was found to be associated with membrane lipid rafts present in the mature sperm, suggesting a role for it in the terminal stages of sperm maturation.

Animals↗
PubMed1999

Time course of cerebrospinal fluid responses to antiretroviral therapy: evidence for variable compartmentalization of infection.

OBJECTIVES: To compare the kinetics and magnitude of HIV-1 RNA responses to antiretroviral therapy (ART) in the cerebrospinal fluid (CSF) and plasma. DESIGN: Repeated lumbar punctures (LPs) were performed after the initiation or change in ART in 15 HIV-1-infected subjects, with the focus on two phases of response: an acute phase within the first 11 days, for which crude estimates of viral RNA half-lives and decay rates were derived and CSF:plasma relative decay ratios quantitatively analysed; and a longer-term phase beyond 4 weeks that was descriptively assessed. RESULTS: In 13 subjects studied during the acute phase, the crude HIV-1 RNA half-life was longer (median 2.0 compared with 1.9 days), the decay rate slower (median 0.13 compared with 0.16 log10 copies/day) and, most notably, the variability greater (intraquartile range of half-life 1.8-4.3 compared with 1.7-2.1 days) in the CSF than in the plasma. A slower decay in the CSF correlated with lower initial blood CD4 T lymphocyte counts (P = 0.001). Seven of 11 subjects studied at 4 weeks or later, including some with slower acute-phase CSF responses, showed greater or more durable viral suppression in the CSF. CONCLUSION: Divergent acute-phase viral kinetics in the CSF and plasma, and proportionally greater long-term decrements in CSF HIV-1 RNA in slow early-responders or poor overall plasma responders indicate variable compartmentalization of CSF infection, consistent with a model of two prototypes of CSF infection: short-lived, transitory infection that predominates in early HIV-1 infection and longer-lived, more autonomous CSF infection predominating in late HIV-1 infection. Additional studies will be needed to define more precisely the acute and longer-term CSF kinetics in different clinical settings and to assess this model.

AIDS Dementia Complex↗
PubMed1999

Compartmentalization of the IgG immune response to HIV-1 in breast milk.

OBJECTIVE: To evaluate the IgG immune response to HIV-1 in colostrum. METHODS: Paired serum and colostrum were collected from 16 asymptomatic HIV-1-infected women. IgG to gp160 and to four peptides (gp41 immunodominant DI domain, gp41/Id; EDLKWA epitope of DIII domain, gp41/K; gp120 C-terminus, gp120/Ct; V3 loop, gp120/V3) were evaluated in all samples. Functional activity of purified IgG was assessed for the ability to block transcytosis of cell-associated HIV-1 through a tight monolayer of endometrial epithelial cell line HEC1. RESULTS: IgG antibody to gp160 and to the four env-encoded synthetic peptides were detected in all specimens. The mean specific activity of IgG to gp41/K was 4.2 fold higher in colostrum than in paired serum. In contrast, mean specific activities of IgG to gp160 and gp41/Id were twofold higher in serum than in paired colostrum. Mean specific activities of IgG to gp120/V3 and to gp120/Ct were similar in systemic and milk compartments. Functional activity of IgG was evaluated in six paired serum and colostrum: in two women, serum IgG was 3.0 and 7.6 fold more efficient in blocking transcytosis than colostrum IgG; in one patient, colostrum IgG exhibited a 28 fold higher inhibitory capacity than serum IgG; in the remaining patients, serum and colostrum IgG demonstrated similar inhibitory activities against transcytosis of HIV. CONCLUSION: These features are consistent with a compartmentalization of the humoral IgG immune response to HIV within the mammary gland. Some HIV-1 antigens are able to induce a strong humoral mucosal immune response which may be of relevance for the design of a mucosal vaccine against HIV-1.

Adolescent↗
PubMed2000

Evidence for late stage compartmentalization of HIV-1 resistance mutations between lymph node and peripheral blood mononuclear cells.

OBJECTIVE: To determine the overall distribution of drug-resistance mutations to nucleoside reverse transcriptase inhibitors of HIV strains recovered from the lymph nodes (LN) and peripheral blood mononuclear cell (PBMC) compartments of four HIV-infected patients receiving zidovudine and didanosine and to compare them with antiretroviral-naive patients. DESIGN: Molecular comparison of major and minor HIV-1 env and pol region variants residing in LN and PBMC compartments. MATERIALS AND METHODS: Proviral DNA sequences were amplified by PCR from both PBMC and LN compartments, cloned into PGEM-T II Easy vector and sequenced. The clones were subjected to molecular and phylogenetic analysis. RESULTS: Comparison of PBMC and LN-derived HIV-1 variants in the env V3 region showed that nucleotide and amino acid variability was a characteristic feature of LN-derived variants. In contrast, a majority of resistance mutations to reverse transcriptase inhibitors were localized in the PBMC compartment rather than in LN, which is thought to be a reservoir of HIV. CONCLUSIONS: Distinct compartmentalization or independent evolution of pol and env gene variants between LN and PBMC could be due to the differential selection pressure imposed by the combination drug regimen, hence the bimodal distribution of resistance variants between LN and PBMC compartments.

Anti-HIV Agents↗
PubMedDate not supplied

An animal model of the compartmental syndrome.

An animal model of the compartmental syndrome is presented to study the effect of elevated intracompartmental pressure on muscle histology and nutrient blood flow. Latex balloons were inserted into the anterior compartment of rabbits and the pressure within them controlled by an adjustable water column. Nutrient blood flow to the muscles of the compartment was determined by an Rb86 isotope dilution technique and showed a progressive decline with intracompartmental pressures over 50 mm Hg. At 80 mm Hg, flow was but 5 per cent of control values. An inflammatory necrosis was noted when a pressure of 60 mm Hg was exerted for 24 hours. At higher pressures an ischemic necrosis without inflammation was observed.

Animals↗
PubMedDate not supplied

The pathophysiology of the anterior tibial compartmental syndrome.

Based on a clinical review of 45 patients with acute anterior tibial ischemia, four different conditions were identified. Three were related to increased pressure within the compartment and were called anterior compartmental syndromes. They followed exercise, trauma, and ischemia. The fourth entity was anterior tibial ischemia due to anterial occlusion. An experimental investigation demonstrated that increased pressure within the anterior compartment slows blood flow to the enclosed tissues.

Anterior Compartment Syndrome↗
PubMedDate not supplied

The anterior and the lateral compartmental syndrome of the leg due to intensive use of muscles.

The anterior and lateral compartmental syndromes of the leg due to intensive use of muscles can be briefly defined as painful circulatory disturbances associated with a pathological increase in total intramuscular pressure. In these syndromes, an acute and a chronic form are distinguished. The acute form takes a progressive course, and the structures within the compartment affected are subject to complete or partial destruction. The chronic form takes an intermittent course. Physical exertion of the lower limbs gives rise to pain in the compartment. Determination of the pressure in the tibialis anteriot muscle and phlebography, both before and after weighted exercise of the muscles of the anterior compartment, were found to be the most valuable diagnostic aids in the chronic syndrome. In the acute syndrome, the compartment affected must be decompressed by fasciotomy as quickly as possible. Since most patients with a chronic syndrome can adequately cope with daily requirements, an operation is not always required. Indications for fasciotomy are presented. The real cause of the increase in total intramuscular pressure is not understood, suggestions concerning the pathogenesis are made, and the mechanism of the circulatory disturbances is discussed.

Acute Disease↗
PubMedDate not supplied

Compartmental syndrome and its relation to the crush syndrome: A spectrum of disease. A review of 11 cases of prolonged limb compression.

A review of 11 cases of prolonged limb compression usually following drug overdose, revealed a spectrum of disease from isolated compartmental syndromes to full crush syndromes with renal failure. Residual limb contractures were moderate or severe in 80 per cent of the extremities involved. Five of the 11 patients demonstrated significant, systematic manifestations, Stage II or Stage III crush syndrome by our definition. The severity of the systemic manifestations is related to the amount of muscle tissue being subjected to elevated pressure and the length of time this pressure is maintained. Delay in hospitalization, delay in diagnosis, and delay in treatment prolong this period. The diagnosis should be made on the basis of the histroy of prolonged immobilization and the finding of a swollen extremity. Fasciotomy should be performed immediately, both to minimize residual limb contracture and to prevent the crush syndrome from developing secondary to myonecrosis.

Acute Kidney Injury↗
PubMedDate not supplied

Compartmental syndromes following trauma.

When an ischemic contracture develops after injury it appears that the ischemia has pursued a middle course between full recovery and gangrene. The mechanism of such a pathology is difficult to understand. There appear to be two distinct types of injury that precipitate such a contracture; one where a major vessel is occluded and the ischemic tissue lies distal to the injury; and a second where the injury is a direct one and the ischemia develops at the site of the injury. The ischemic changes that develop after both types of injury appear to be remarkably similar and they develop, almost exclusively, where the tissues involved lie within unyielding osteofascial compartment. In both types, compartmental syndrome could have been precipitated; on the one hand by the ischemia of arterial interruption and on the other by direct tissue damage. Early fasciotomy is advocated after both types of injury, quite apart from any necessary arterial repair.

Anterior Compartment Syndrome↗
PubMed1989

Serial allometric factor extrapolation: compartmental and physiological pharmacokinetic approaches.

Interspecies dose-response equivalence is most frequently estimated as the product of a reference species dose and a single scaling ratio based on a physiological parameter such as body weight, body surface area, maximum lifespan potential, DNA repair rate, etc. This approach may suffice for certain narrowly defined applications but is likely to be inadequate or inappropriate for many others. A biologically plausible rationale for these inadequacies and for their resolution can be demonstrated using a structured approach to dose scaling, termed serial allometric factor extrapolation (SAFE). The SAFE procedure is unique in that variations in chemical-specific toxic interaction mechanisms can be incorporated into the scaling process. The compartmental and physiological pharmacokinetic (PPK) bases for the procedure are demonstrated using published data on acute intravenous toxicity of chemotherapeutic agents in animals and humans. The interrelationships of SAFE equations, PPK, and regression allometry of dose response are discussed.

Animals↗
PubMed1985

Plantar compartmental infection in the diabetic foot. The role of computed tomography.

This review discusses the role of computed tomography (CT) in the evaluation of extent of plantar soft tissue infection in the diabetic foot. CT abnormalities are correlated with conventional radiography, results of preoperative aspiration cultures, intraoperative assessment, and bone, gallium, and 111In-leukocyte scan findings. Plantar soft tissue disease respects compartmental boundaries in general, with transcompartmental spread possible along musculotendinous units that normally transgress the intervening fascial septae. CT correlates well with the extent of infection as determined by other modalities, but cannot precisely predict its proximal boundary due to gradual transition between unequivocally abnormal and normal tissue. CT may be useful in establishing an appropriate level for contemplated amputation and can detect extension of superficial diabetic foot infections at an earlier stage than existing clinical methods, potentially resulting in less extensive surgical procedures.

Bacterial Infections↗
PubMed1994

Treatment of compartmental liquefaction as a late sequelae of a lower limb compartment syndrome.

Symptomatic liquefaction and calcification of muscle tissue as a late sequela of compartment syndrome of the lower leg is rare. The literature shows a high complication rate involved with simple debridement of these compartments. In our limited experience, complete compartmental debridement and immediate introduction of functional viable muscle may prevent the documented complications of chronic drainage and infection.

Adult↗
PubMed1999

Near-infrared spectroscopy: a potential method for continuous, transcutaneous monitoring for compartmental syndrome in critically injured patients.

BACKGROUND: Near-infrared spectroscopy (NIRS) noninvasively measures tissue O2 saturation (StO2), and has been proposed as a means of monitoring for compartmental syndrome (CS). However, its specificity in hypoxemic, hypotensive patients with severely reduced systemic oxygen delivery has not been tested. We hypothesized that NIRS can differentiate muscle ischemia caused by shock from ischemia caused by CS. METHODS: Nine swine were anesthetized and an NIRS probe placed over the anterolateral compartment of the hind leg. Compartment pressure was also measured. A nerve stimulator was placed over the peroneal nerve, and CS was defined as loss of dorsiflexion twitch. At 30-minute sequential intervals, mean arterial blood pressure was reduced to 60% of baseline (phlebotomy), fraction of inspired oxygen was reduced to 0.15, and compartment pressure was increased in one limb by interstitial albumin infusion until CS occurred. RESULTS: Hypotension combined with hypoxemia reduced StO2 from 82+/-4% to 66+/-10%. CS further reduced StO2 to 16+/-12% (p<0.0001). During hypotension + hypoxemia + CS, control limb StO2 was 70+/-15% (p = 0.0002 vs. experimental limb). CONCLUSION: NIRS detects muscle ischemia caused by CS despite severe hypotension and hypoxemia, making it potentially useful in critically injured, unstable patients.

Animals↗
PubMed2001

Near-infrared spectroscopy versus compartment pressure for the diagnosis of lower extremity compartmental syndrome using electromyography-determined measurements of neuromuscular function.

BACKGROUND: Compartmental syndrome (CS) is difficult to diagnose in intensive care unit patients. Compartment perfusion pressure (CPP) is an invasive, indirect measure of ischemia. Near-infrared spectroscopy is noninvasive, and directly measures ischemia by transmitting light through tissues at wavelengths that react with hemoglobin to provide percent tissue oxygen saturation (Sto(2)). Animal studies demonstrate that Sto(2) is superior to CPP for detecting CS. However, there are no studies in humans comparing Sto(2) with CPP. We hypothesized that Sto(2) can reliably detect CS, and is superior to CPP. METHODS: CS was induced in 15 human volunteers using a standard calf compression model. At 30-minute intervals, compression was increased to reduce Sto(2) from baseline (86% +/- 4%) to 60%, 40%, 20%, and < 10%, with simultaneous recording of CPP. Outcome variables included deep peroneal nerve conduction assessed by electromyography, cutaneous peroneal nerve sensitivity using Semmes-Weinstein monofilaments, and pain (visual analog scale). RESULTS: Both Sto(2) and CPP significantly correlated with all ischemia outcome variables (p < 0.001). Receiver operating characteristic curves of deep peroneal nerve conduction demonstrated that Sto(2) had higher sensitivity than CPP for detecting > 50% block. For example, when specificity was 83% for Sto(2) and 84% for CPP, sensitivity was 85% versus 56%, respectively (p = 0.02). When specificity for both was 72%, sensitivity was 94% for Sto(2) versus 76% for CPP (p = 0.04). CONCLUSION: In intensive care unit patients who cannot alert physicians to symptoms, near-infrared spectroscopy may help clinicians to avoid delayed or unnecessary prophylactic fasciotomy, and provides the benefits of a continuous, noninvasive monitoring technique.

Adolescent↗
PubMed1997

Compartmental shifts of calcium and magnesium as a result of swimming and swimming training in rats.

To describe accurately the mineral changes (Ca and Mg) provoked by swimming, the aims of this study were to analyze those tissues that, with regard to their mineral content, can better classify individuals performing both swimming until exhaustion and swimming as training and to know the shifts of these minerals between different tissues after a single session of swimming until exhaustion and after training. Wistar rats were distributed into 12 groups, six male and six female (N = 10): 1) control rest group (CR); 2) trained rest group (TR); 3) control exercise group (CE); 4) trained exercise group (TE); 5) control recovery group (CER) and 6) trained recovery group (TER). The most informative tissues of Ca and Mg compartmental shifts during exercise have been determined. Discriminant analysis selected heart Ca, muscle Ca and bone Ca, bone Mg, erythrocyte Mg, and serum Mg as the most significant variables. The animals were classified by means of two canonical axes: the first one relates to training situation and sex, and the second one shows the special characteristics of trained male rats. Another independent discriminant analysis applied to male and female groups separately showed that the first canonical axis (control/trained) is basically defined by heart Ca, bone Ca, and erythrocyte Mg (male), and by heart Ca, bone Ca, and bone Mg (female), while the second axis, related to the exercise situations, is defined by the serum Mg levels in both sexes. We think that discriminant analysis is a statistical method capable of explaining physiological processes and classifying individuals performing exercises of different length. It suggests that the homeostasis of Ca and Mg is somewhat different for males and females. Serum magnesium must be considered to distinguish exercise situations. The analysis of these tissues could inform us about the mineral status of the rats and then we could correct possible deficiencies in our research. In this work we have only found different mineral redistributions among tissues. The trained animals have a better mineral recovery capacity than the untrained ones. Training has a different physiological repercussion in male and female rats on the basis of their respective maximal swimming times after training and their mineral behavior.

Animals↗
PubMed1991

An experimental compartmental flow model for assessing the hemodynamic response of intracranial arteriovenous malformations to stereotactic radiosurgery.

Stereotactic radiosurgery has proven to be an effective method of treating selected inaccessible or inoperable arteriovenous malformations (AVMs) of the brain. Radiation-induced obliteration of successfully-treated AVMs, however, occurs only after some latent period after treatment, depending on size, location, and dose. An experimental compartmental flow model is proposed to describe the hemodynamic alterations in the AVM as a result of the pathophysiological changes after radiosurgery, and to analyze temporal alterations in AVM blood flow rates and pressure gradients before complete obliteration. In representative small (low-flow, 150 ml/min) and large (high-flow, 440 ml/min) AVMs, it is found that increases in pressure gradients across certain vascular structures within the AVM occur during the normal course of radiation-induced flow decrease and AVM obliteration. The magnitude of these pressure alterations, however, may be within the normal physiological variations in cerebrovascular blood pressure. The effects of partial-volume irradiation of the AVM is examined by limiting radiosurgical treatment to varying portions of the flow compartments within the model. It is found that alterations in pressure gradients persist in unirradiated vascular shunts, even after complete obliteration of the treated AVM volume. These pressure alterations may increase the probability of hemorrhage from the untreated shunts of the AVM and cause redistribution of regional cerebral blood flow resulting in increased flow through these untreated shunts.

Cerebrovascular Circulation↗
PubMed2001

Physiological significance of the rate constants in compartmental analysis.

Transfer (rate) constants in compartmental analysis are generally considered solely in operational terms, and little attention has been paid to their physiological interpretation. In this study we have examined the significance of their roles in physiological terms and the implications of this interpretation. When freely diffusible tracers are introduced into the blood stream by bolus injection, the sum of the exit rate constants from the blood compartment gives the number of blood volumes turned over per unit time; when multiplied by the blood volume, this value is the cardiac output. When corrected for body weight, the product yields the cardiac index, a biological constant for large mammals. The ratio of the rate constant supplying an organ to the exit-constant sum gives fractional cardiac output, and when multiplied by the cardiac output the ratio gives organ blood flow, independent of diffusibility. For freely diffusible tracers, organ blood flow can be calculated directly from the product of the organ rate constant and blood volume. At equilibrium and at equal concentration, the ratio of rate constants between adjacent compartments gives their relative volumes; this interpretation is fundamental when partitioning compartments for detailed analysis. These considerations have been validated by testing in both animals and man. Multiple solution sets may occur in mammillary models. Knowledge of the physiological interpretation of intercompartmental rate constants is of importance not only in model interpretation but in model validation, where this information serves as an independent check on model structure and its realization.

Animals↗
PubMed1994

Compartmentation of whole brain blood flow and oxygen and glucose metabolism in monkeys.

The cerebral metabolic rate of oxygen (CMRO2) has been functionally compartmentalized using the barbiturate thiopental into active CMRO2, associated with electroencephalographic (EEG) activity, and the balance, basal CMRO2, associated with the maintenance of neuronal viability. Previous measurements of these CMRO2 compartments were made in anesthetized animals. Our aim was to determine whether the same proportions for these compartments applied in unanesthetized monkeys. The active: basal distribution of the cerebral metabolic rate of glucose (CMRG) and cerebral flood flow (CBF) were also determined. Three measurements of whole-brain CBF (H2 clearance), CMRO2, and CMRG were made in six unanesthetized rhesus monkeys (Macaca mulatta). Thereafter, thiopental anesthesia was induced and maintained until an isoelectric EEG was obtained. Three additional measurements of CBF, CMRO2, and CMRG were made. Arterial blood pressure, end-tidal CO2, and arterial blood gas were measured with each set of measurements. Thiopental-induced isoelectric EEG resulted in a 47% reduction in CMRO2 from 5.95 +/- 0.54 to 3.10 +/- 0.51 ml/100 g/min (mean +/- SD); a 36% reduction in CBF from 76 +/- 21 to 48 +/- 14 ml/100 g/min; and a 61% reduction in CMRG from 8.09 +/- 2.78 to 3.13 +/- 0.77 mg/100 g/min. The oxygen-glucose index was 0.99 +/- 0.10 for the whole brain, 0.87 +/- 0.15 for the active, and 1.27 +/- 0.25 for the basal compartments. These results indicated an active:basal distribution of approximately 50:50 for CMRO2, 40:60 for CBF, and 60:40 for CMRG. The active:basal CMRO2 distribution corroborates earlier data and shows that relative to CMRO2, the active compartment is underperfused with a lower oxygen-glucose index compared with the basal compartment.

Anesthesia↗