Absorption and pharmacokinetics of green tea catechins in beagles

The present study evaluates for the first time in dogs, the kinetics of green tea catechins and their metabolic forms in plasma and urine. Ten beagles were administered 173 mg (12·35 mg/kg body weight) of catechins as a green tea extract, in capsules. Blood samples were collected during 24 h after intake and urine samples were collected during the following periods of time: 0-2, 2-6, 6-8 and 8-24 h. Two catechins with a galloyl moiety and three conjugated metabolites were detected in plasma. Most of the detected forms in plasma reached their maximum plasma concentration (Cmax) at around 1 h. Median Cmax for (2)-epigallocatechin-3-gallate (EGCG), (2)-epicatechin-3-gallate (ECG), (2)-epigallocatechin glucuronide (EGCglucuronide), (2)-epicatechin glucuronide (EC-glucuronide), (2)-epicatechin sulphate (EC sulphate) were 0·3 (range 0·1-1·9), 0·1 (range 0-0·4), 0·8 (range 0·2-3·9), 0·2 (range 0·1 1·7) and 1 (range 0·3-3·4) mmol/l, respectively. The areas under the plasma concentration v. time curves (AUC0!24) were 427 (range 102-1185) mmol/l £ min for EGC-glucuronide, 112 (range 53-919) mmol/l £ min for EC-sulphate, 71 (range 26-306) mmol/l £ min for EGCG, 40 (range 12-258) mmol/l £ min for EC-glucuronide and 14 (range 0·1-124) mmol/l £ min for ECG. The values of mean residence time (MRT0!24) were 5 (range 2-16), 2 (range 1-11), 10 (range 2-13), 3 (range 2-16) and 2·4 (range 1-18) h for EGCG, ECG, EGC-glucuronide, EC-glucuronide and EC sulphate, respectively. In urine, catechins were present as conjugated forms, suggesting bile excretion of EGCG and ECG. Green tea catechins are absorbed following an oral administration and EGC-glucuronide is the metabolic form that remains in the organism for a longer period of time, suggesting that this compound could suffer an enterohepatic cycle.

Absorption and pharmacokinetics of green tea catechins in beagles

The present study evaluates for the first time in dogs, the kinetics of green tea catechins and their metabolic forms in plasma and urine. Ten beagles were administered 173 mg (12·35 mg/kg body weight) of catechins as a green tea extract, in capsules. Blood samples were collected during 24 h after intake and urine samples were collected during the following periods of time: 0-2, 2-6, 6-8 and 8-24 h. Two catechins with a galloyl moiety and three conjugated metabolites were detected in plasma. Most of the detected forms in plasma reached their maximum plasma concentration (Cmax) at around 1 h. Median Cmax for (2)-epigallocatechin-3-gallate (EGCG), (2)-epicatechin-3-gallate (ECG), (2)-epigallocatechin glucuronide (EGCglucuronide), (2)-epicatechin glucuronide (EC-glucuronide), (2)-epicatechin sulphate (EC sulphate) were 0·3 (range 0·1-1·9), 0·1 (range 0-0·4), 0·8 (range 0·2-3·9), 0·2 (range 0·1 1·7) and 1 (range 0·3-3·4) mmol/l, respectively. The areas under the plasma concentration v. time curves (AUC0!24) were 427 (range 102-1185) mmol/l £ min for EGC-glucuronide, 112 (range 53-919) mmol/l £ min for EC-sulphate, 71 (range 26-306) mmol/l £ min for EGCG, 40 (range 12-258) mmol/l £ min for EC-glucuronide and 14 (range 0·1-124) mmol/l £ min for ECG. The values of mean residence time (MRT0!24) were 5 (range 2-16), 2 (range 1-11), 10 (range 2-13), 3 (range 2-16) and 2·4 (range 1-18) h for EGCG, ECG, EGC-glucuronide, EC-glucuronide and EC sulphate, respectively. In urine, catechins were present as conjugated forms, suggesting bile excretion of EGCG and ECG. Green tea catechins are absorbed following an oral administration and EGC-glucuronide is the metabolic form that remains in the organism for a longer period of time, suggesting that this compound could suffer an enterohepatic cycle.

Cerebral Hypoperfusion in Posterior Reversible Encephalopathy Syndrome is Different from Transient Ischemic Attack on CT Perfusion.

BACKGROUND: PRES is a reversible neurotoxic state presenting with headache, altered mental status, visual loss, and seizures. Delayed diagnosis can be avoided if radiological patterns could distinguish PRES from cerebral ischemia. METHODS: Clinical and radiological data were collected on all hospitalized patients who had (1) discharge diagnosis of PRES and (2) acute CTP/CTA. Data were compared with 10 TIA patients with proven cytotoxic edema on MRI. RESULTS: Of the four PRES patients found, three were correlated with acute blood pressure and one with chemotherapy. At the radiological level, quantitative analyses of the CTP parameters showed that 2 out of 4 patients had bilaterally reduced CBF-values (23.2-47.1 ml/100g/min) in occipital regions, as seen in the pathological regions of TIA patients (27.3 ± 13.5 ml/100g/min). When compared with TIA patients, the pathological ROI's demonstrated decreased CBV-values (3.4-5.6 ml/100g). Vasogenic edema on MRI FLAIR imaging was seen in only one PRES patient, and cytotoxic edema on DWI-imaging was never found. CT angiography showed in one PRES patient a vasospasm-like unilateral posterior cerebral artery. CONCLUSIONS: If confirmed by other groups, CTP and CTA imaging in patients with acute visual loss and confusion may help to distinguish PRES from bi-occipital ischemia. These radiological parameters may identify PRES patients at risk for additional tissue infarction.

Transient ocular motor nerve palsies associated with presumed cranial nerve schwannomas.

BACKGROUND: Cranial nerve schwannomas are radiologically characterized by nodular cranial nerve enhancement on magnetic resonance imaging (MRI). Schwannomas typically present with gradually progressive symptoms, but isolated reports have suggested that schwannomas may cause fluctuating symptoms as well. METHODS: This is a report of ten cases of presumed cranial nerve schwannoma that presented with transient or recurring ocular motor nerve deficits. RESULTS: Schwannomas of the third, fourth, and fifth nerves resulted in fluctuating deficits of all 3 ocular motor nerves. Persistent nodular cranial nerve enhancement was present on sequential MRI studies. Several episodes of transient oculomotor (III) deficts were associated with headaches, mimicking ophthalmoplegic migraine. CONCLUSIONS: Cranial nerve schwannomas may result in relapsing and remitting cranial nerve symptoms.

Protein loop compaction and the origin of the effect of arginine and glutamic acid mixtures on solubility, stability and transient oligomerization of proteins

Addition of a 50 mM mixture of l-arginine and l-glutamic acid (RE) is extensively used to improve protein solubility and stability, although the origin of the effect is not well understood. We present Small Angle X-ray Scattering (SAXS) and Nuclear Magnetic Resonance (NMR) results showing that RE induces protein compaction by collapsing flexible loops on the protein core. This is suggested to be a general mechanism preventing aggregation and improving resistance to proteases and to originate from the polyelectrolyte nature of RE. Molecular polyelectrolyte mixtures are expected to display long range correlation effects according to dressed interaction site theory. We hypothesize that perturbation of the RE solution by dissolved proteins is proportional to the volume occupied by the protein. As a consequence, loop collapse, minimizing the effective protein volume, is favored in the presence of RE.

Transient detectable viremia and the risk of viral rebound in patients from the Swiss HIV Cohort Study.

BACKGROUND: Temporary increases in plasma HIV RNA ('blips') are common in HIV patients on combination antiretroviral therapy (cART). Blips above 500 copies/mL have been associated with subsequent viral rebound. It is not clear if this relationship still holds when measurements are made using newer more sensitive assays. METHODS: We selected antiretroviral-naive patients that then recorded one or more episodes of viral suppression on cART with HIV RNA measurements made using more sensitive assays (lower limit of detection below 50 copies/ml). We estimated the association in these episodes between blip magnitude and the time to viral rebound. RESULTS: Four thousand ninety-four patients recorded a first episode of viral suppression on cART using more sensitive assays; 1672 patients recorded at least one subsequent suppression episode. Most suppression episodes (87 %) were recorded with TaqMan version 1 or 2 assays. Of the 2035 blips recorded, 84 %, 12 % and 4 % were of low (50-199 copies/mL), medium (200-499 copies/mL) and high (500-999 copies/mL) magnitude respectively. The risk of viral rebound increased as blip magnitude increased with hazard ratios of 1.20 (95 % CI 0.89-1.61), 1.42 (95 % CI 0.96-2.19) and 1.93 (95 % CI 1.24-3.01) for low, medium and high magnitude blips respectively; an increase of hazard ratio 1.09 (95 % CI 1.03 to 1.15) per 100 copies/mL of HIV RNA. CONCLUSIONS: With the more sensitive assays now commonly used for monitoring patients, blips above 200 copies/mL are increasingly likely to lead to viral rebound and should prompt a discussion about adherence.

Acute Lyme Neuroborreliosis With Transient Hemiparesis and Aphasia.

Nervous system involvement in Lyme disease often mimics other conditions and thus represents a diagnostic challenge, especially in an emergency department setting. We report a case of a female teenager presenting with sudden-onset aphasia and transient right-sided faciobrachial hemiplegia, along with headache and agitation. Ischemia, vasculitis, or another structural lesion was excluded by brain imaging. Toxicologic evaluation results were negative. Cerebral perfusion computed tomography and electroencephalography showed left parietotemporal brain dysfunction. Lumbar puncture result, although atypical, suggested bacterial infection and intravenous ceftriaxone was initiated. Finally, microbiological cerebrospinal fluid analysis revealed Lyme neuroborreliosis, showing specific intrathecal antibody production and high level of C-X-C motif chemokine 13. The patient rapidly recovered. To our knowledge, this report for the first time illustrates that acute-onset language and motor symptoms may be directly related to Lyme neuroborreliosis. Neuroborreliosis may mimic other acute neurologic events such as stroke and should be taken into diagnostic consideration even in the absence of classic symptoms and evolution.

CTP in Transient Global Amnesia: A Single-Center Experience of 30 Patients.

BACKGROUND AND PURPOSE: Medial temporal lobe abnormalities on DWI and functional imaging are occasionally observed in patients with transient global amnesia. We used CTP to study these patients during or briefly after resolution of their amnesic syndrome. MATERIALS AND METHODS: From 2002 onward, patients satisfying clinical criteria for transient global amnesia who underwent CTP were included. Patients with additional clinical features suggesting transient ischemic attack or stroke and those with an ischemic lesion on subsequent DWI were excluded. If deemed necessary by the clinician, DWI was performed within 10 days. RESULTS: Thirty patients with transient global amnesia underwent CTP at a median latency of 5.9 hours (interquartile range, 4.3-9.7 hours) after symptom onset. All findings, except for those in 1 patient, were normal, including those in the 14 patients with well-imaged hippocampi. In the patient with abnormal findings, CTP and PWI showed hypoperfusion in both lentiform nuclei extending into the insulae, with normalization on the repeat CTP 6 days later. In 10 patients, DWI was performed at a median latency of 2 days (interquartile range, 0-9 days). Of these, 2 showed punctate hippocampal lesions, often seen in transient global amnesia. In 2 patients excluded because of mildly atypical transient global amnesia and ischemic lesions on subsequent DWI, acute CTP findings were also normal. CONCLUSIONS: Patients with transient global amnesia had normal CTP findings in the acute phase with the exception of 1 patient with transient hypoperfusion in both basal ganglia. If imaging is performed for typical and atypical transient global amnesia, DWI should be the preferred method.

Transient shear banding in time-dependent fluids

We study the dynamics of shear-band formation and evolution using a simple rheological model. The description couples the local structure and viscosity to the applied shear stress. We consider in detail the Couette geometry, where the model is solved iteratively with the Navier-Stokes equation to obtain the time evolution of the local velocity and viscosity fields. It is found that the underlying reason for dynamic effects is the nonhomogeneous shear distribution, which is amplified due to a positive feedback between the flow field and the viscosity response of the shear thinning fluid. This offers a simple explanation for the recent observations of transient shear banding in time-dependent fluids. Extensions to more complicated rheological systems are considered.

Using transient elastography to detect chronic liver diseases in a primary care nurse consultancy

Background: Chronic liver diseases (CLDs) are significant causes of death in adults in many countries and are usually diagnosed at late stages. Early detection may allow time for treatment to prevent disease progression. Objectives: The aim of this study was to assess the feasibility of screening for unrecognized CLDs in a primary care nurse consultancy and report findings from screening. Methods: Two experienced nurses in a primary care nurse consultancy were trained to perform transient elastography (TE). Subjects aged from 18 to 70 years were identified randomly from the health registry and invited to participate in a feasibility pilot study. Exclusion criteria were past or current history of liver diseases. Nurses collected demographic and clinical data and performed TE tests using Fibroscan tomeasure liver stiffness; a cutoff score of 6.8 kPa or greater was used as an indicator of the presence of CLD with fibrosis. Results: Accurate measurements were obtained in 495 of 502 participants (98.6%). Prevalence of elevated liver stiffness was observed in 28 of 495 subjects (5.7%). Compared to patients with normal liver stiffness, patients with increased liver stiffness were older, were more frequently male, and had higher frequency of metabolic syndrome. Nonalcoholic fatty liver was the most common cause of CLD. Discussion: Following training in procedures for conducting TE, nurses in a primary care clinic were able to detect unrecognized CLDs in presumably healthy subjects. Early detection of CLDs is feasible in primary care clinics and may facilitate identification of undiagnosed CLD in adults.

Combinación de sistemas de flujo de baja y alta presion para la determinacion de Mg, Ca y Sr en salmueras por espectrofotometria de absorcion atomica con llama

This article describes the combination of low- and high-pressure flow systems for the determination of Magnesium, Calcium and Strontium by flame atomic absorption spectrometry (FAAS). In the low-pressure system a short C-18 RP column (length 0,5 cm) was utilized for the preconcentration/matrix separation step, xylenol orange was used as chelating agent and tetrabutylamonium acetate for ion pair formation. The hydraulic high pressure nebulization (HHPN) was used for sample transport and sample introduction in the high pressure system. The repeatabilities and detection limits for Mg, Ca and Sr were determined and compared with those obtained by pneumatic nebulization (PN). The results show that the detection limits obtained using the HHPN for Mg, Ca and Sr are between 1.5 to 2 times better than those obtained by PN when the signal transient was measured in area. The system presented a sampling frequency of 130 h-1 for direct determination of Mg, Ca or Sr in samples of saturated sodium chloride used in the production of chlorine and sodium hydroxide.

Random walk radiosity with generalized absorption probabilities

The author studies random walk estimators for radiosity with generalized absorption probabilities. That is, a path will either die or survive on a patch according to an arbitrary probability. The estimators studied so far, the infinite path length estimator and finite path length one, can be considered as particular cases. Practical applications of the random walks with generalized probabilities are given. A necessary and sufficient condition for the existence of the variance is given, together with heuristics to be used in practical cases. The optimal probabilities are also found for the case when one is interested in the whole scene, and are equal to the reflectivities