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1.
Metab Eng ; 61: 315-325, 2020 09.
Article in English | MEDLINE | ID: mdl-32687991

ABSTRACT

One-carbon (C1) compounds, such as methanol, have recently gained attention as alternative low-cost and non-food feedstocks for microbial bioprocesses. Considerable research efforts are thus currently focused on the generation of synthetic methylotrophs by transferring methanol assimilation pathways into established bacterial production hosts. In this study, we used an iterative combination of dry and wet approaches to design, implement and optimize this metabolic trait in the most common chassis, E. coli. Through in silico modelling, we designed a new route that "mixed and matched" two methylotrophic enzymes: a bacterial methanol dehydrogenase (Mdh) and a dihydroxyacetone synthase (Das) from yeast. To identify the best combination of enzymes to introduce into E. coli, we built a library of 266 pathway variants containing different combinations of Mdh and Das homologues and screened it using high-throughput 13C-labeling experiments. The highest level of incorporation of methanol into central metabolism intermediates (e.g. 22% into the PEP), was obtained using a variant composed of a Mdh from A. gerneri and a codon-optimized version of P. angusta Das. Finally, the activity of this new synthetic pathway was further improved by engineering strategic metabolic targets identified using omics and modelling approaches. The final synthetic strain had 1.5 to 5.9 times higher methanol assimilation in intracellular metabolites and proteinogenic amino acids than the starting strain did. Broadening the repertoire of methanol assimilation pathways is one step further toward synthetic methylotrophy in E. coli.


Subject(s)
Alcohol Oxidoreductases , Aldehyde-Ketone Transferases , Bacterial Proteins , Escherichia coli , Fungal Proteins , Metabolic Engineering , Methanol/metabolism , Alcohol Oxidoreductases/genetics , Alcohol Oxidoreductases/metabolism , Aldehyde-Ketone Transferases/genetics , Aldehyde-Ketone Transferases/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Escherichia coli/genetics , Escherichia coli/metabolism , Fungal Proteins/genetics
2.
J Interv Card Electrophysiol ; 63(1): 133-142, 2022 Jan.
Article in English | MEDLINE | ID: mdl-33570717

ABSTRACT

PURPOSE: Ablation index (AI) is a radiofrequency lesion quality marker. The AI value that allows effective and safe pulmonary vein isolation (PVI) is still debated. We evaluated the incidence of acute and late PV reconnection (PVR) with different AI settings and its predictors. METHODS: The Ablation Index Registry is a multicenter study that included patients with paroxysmal/persistent atrial fibrillation (AF) who underwent first-time ablation. Each operator performed the ablation using his preferred ablation catheter (ThermoCool® SmartTouch or Surround Flow) and AI setting (380 posterior-500 anterior and 330 posterior-450 anterior). We divided the study population into two groups according to the AI setting used: group 1 (330-450) and group 2 (380-500). Incidence of acute PVR was validated within 30 min after PVI, whereas the incidence of late PVR was evaluated at repeat procedure. RESULTS: Overall, 490 patients were divided into groups 1 (258) and 2 (232). There was no significant difference in the procedural time, fluoroscopy time, and rate of the first-pass PVI between the two study groups. Acute PVR was observed in 5.6% PVs. The rate of acute PVR was slightly higher in group 2 (64/943, 6.8%, PVs) than in group 1 (48/1045, 4.6% PVs, p = 0.04). Thirty patients (6%) underwent a repeat procedure and late PVR was observed in 57/116 (49%) PVs (number of reconnected PV per patient of 1.9 ± 1.6). A similar rate of late PVR was found in the two study groups. No predictors of acute and late PVR were found. CONCLUSION: Ablation with a lower range of AI is highly effective and is not associated with a higher rate of acute and late PVR. No predictors of PV reconnection were found.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Pulmonary Veins , Atrial Fibrillation/diagnostic imaging , Atrial Fibrillation/surgery , Humans , Pulmonary Veins/diagnostic imaging , Pulmonary Veins/surgery , Recurrence , Treatment Outcome
3.
Front Chem ; 9: 741876, 2021.
Article in English | MEDLINE | ID: mdl-34805090

ABSTRACT

With the aim of developing an in vitro model for the bioavailability (BA) prediction of drugs, we focused on the study of levonorgestrel (LVN) released by 1.5 mg generic and brand-name tablets. The developed method consisted in combining a standard dissolution test with an optimized parallel artificial membrane permeability assay (PAMPA) to gain insights into both drug release and gastrointestinal absorption. Interestingly, the obtained results revealed that the tablet standard dissolution test, combined with an optimized PAMPA, highlighted a significant decrease in the release (15 ± 0.01 µg min-1 vs 30 ± 0.01 µg min-1) and absorption (19 ± 7 × 10-6 ± 7 cm/s Pe vs 41 ± 15 × 10-6 cm/s Pe) profiles of a generic LVN tablet when compared to the brand-name formulation, explaining unbalanced in vivo bioequivalence (BE). By using this new approach, we could determine the actual LVN drug concentration dissolved in the medium, which theoretically can permeate the gastrointestinal (GI) barrier. In fact, insoluble LVN/excipient aggregates were found in the dissolution media giving rise to non-superimposable dissolution profiles between generic and brand-name LVN tablets. Hence, the results obtained by combining the dissolution test and PAMPA method provided important insights confirming that the combined methods can be useful in revealing crucial issues in the prediction of in vivo BE of drugs.

4.
J Pharm Biomed Anal ; 198: 113985, 2021 May 10.
Article in English | MEDLINE | ID: mdl-33667833

ABSTRACT

A new chromatographic method by Ultra High Performance Liquid Chromatographic (UHPLC) technology, has been developed and validated for the determination of polydatin and resveratrol, as potential metabolite, in human plasma. After the optimization of the chromatographic conditions, the method has been validated on spiked human plasma samples. The optimized extraction allowed to obtain analytes recovery up to 98.48 ± 4.03 %. Then, the isocratic elution in reversed phase mode, provides the separation of polydatin and resveratrol in less than 10.0 min. Chromatographic analysis was performed on a C18, 10 cm x 3.0 mm, 2.7 µm stationary phase, by using triethanolamine phosphate solution (0.1 M, pH = 3.7) and ACN 85:15 (v/v) as mobile phase at a flow rate of 0.5 mL/min. The UV detector was set at 306 nm for the analysis of both polydatin and resveratrol. The limit of detection (LoD) and the limit of quantification (LoQ) for polydatin in plasma samples were found to be 7.82 ± 0.38 nM and 26.06 ± 1.28 nM respectively. The method was found to be accurate and precise with a coefficient for intra- and inter-day variation below 5 %. All the reported data demonstrate how the developed method is rapid and sensitive. Moreover, results of the analysis of plasma samples, obtained from orally treated volunteers with nutritional supplements containing polydatin, have shown the method to be suitable for the pharmacokinetic characterization of polydatin and resveratrol, as metabolite, in humans.


Subject(s)
Glucosides , Stilbenes , Chromatography, High Pressure Liquid , Humans , Plasma/chemistry , Reproducibility of Results , Stilbenes/analysis
5.
Clin Transl Oncol ; 23(8): 1561-1570, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33570720

ABSTRACT

PURPOSE: Radiosurgery (SRS) is an effective treatment option for brain metastases (BMs). Long-term results of the first worldwide experience with a mono-isocentric, non-coplanar, linac-based stereotactic technique in the treatment of multiple BMs are reported. METHODS: patients with multiple BMs, life expectancy > 3 months, and good performance status (≤ 2) were treated with simultaneous SRS with volumetric modulated arc technique. Data were retrospectively evaluated. RESULTS: 172 patients accounting for 1079 BMs were treated at our institution from 2017 to 2020. The median number of treated metastases was 4 (range 2-22). Primary tumor histology was: lung (44.8%), breast (32%), and melanoma (9.4%). The 2-year LPFS was 71.6%, respectively. A biological effective dose (BED) ≥ 51.3 Gy10 correlated with higher local control. Uncontrolled systemic disease and melanoma histology were independent prognostic factors correlated with decreased iPFS. Patients with > 10 BMs had a trend towards shorter iPFS (p = 0.055). 31 patients received multiple SRS courses (2-7) in case of intracranial progression. The median iOS was 22.4 months. Brainstem metastases and total PTV > 7.1 cc correlated with shorter iOS. The 1- and 2-year WBRT-free survival was 83.2% and 61.1%, respectively. CONCLUSION: Long-term results in a large patient population treated with a mono-isocentric, dedicated technique demonstrated its effectiveness and safety also in the case of multiple courses. The shortened treatment time and the possibility to safely spare healthy brain tissue allows the safe treatment of patients with a large number of metastases and to deliver multiple courses of SRS. In selected cases, the administration of WBRT can be delayed.


Subject(s)
Brain Neoplasms/radiotherapy , Brain Neoplasms/secondary , Cranial Irradiation/methods , Radiosurgery/methods , Adult , Aged , Aged, 80 and over , Brain Neoplasms/mortality , Breast Neoplasms/pathology , Cohort Studies , Cranial Irradiation/adverse effects , Cranial Irradiation/instrumentation , Female , Humans , Kaplan-Meier Estimate , Lung Neoplasms/pathology , Male , Melanoma/radiotherapy , Melanoma/secondary , Middle Aged , Neoplasm Recurrence, Local/radiotherapy , Organs at Risk/radiation effects , Progression-Free Survival , Radiation Injuries/prevention & control , Radiosurgery/adverse effects , Radiosurgery/instrumentation , Radiotherapy Dosage , Relative Biological Effectiveness , Retrospective Studies , Time Factors , Treatment Outcome
6.
J Neurosci Methods ; 338: 108685, 2020 05 15.
Article in English | MEDLINE | ID: mdl-32173400

ABSTRACT

Aggregates of alpha-synuclein (αSyn) have been described in Parkinson's disease (PD) patients, and recent evidence has suggested that the most toxic αSyn species in PD are small soluble aggregates including oligomers, prefibrils, protofibrils. The physiological function of αSyn is still highly debated, with a possible role in synaptic vesicle trafficking and release at the presynaptic compartment, and in the regulation of gene expression in the nucleus. Emerging evidence indicate that most of αSyn functions are related with the crucial ability to bind biological membranes, which is associated with structural conversion from a disordered monomer to an α-helical enriched structure. Conformational properties of αSyn can be modulated by a number of factors including post-translational modifications, gene duplication and triplication-driven overexpression, single point mutations, environmental changes, which affect membrane binding and the protein propensity to aggregate in toxic species. The recognized toxic role of αSyn in PD has laid the rational for purposing of αSyn-based, neuropathologically relevant preclinical models of PD. Different approaches have led to the establishment of transgenic models, viral vector-based models, and more recently models based on the intracerebral inoculation of exogenous αSyn preformed fibrils/oligomers. Here, we overview and compare viral vector-based models of αSyn overexpression and models obtained by direct intracerebral infusion of in vitro preformed αSyn species. The advantages and pitfalls associated with these different approaches are discussed.


Subject(s)
Parkinson Disease , alpha-Synuclein , Animals , Humans , Parkinson Disease/genetics , Rodentia , Viruses , alpha-Synuclein/genetics
7.
Proc Math Phys Eng Sci ; 475(2227): 20190178, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31423098

ABSTRACT

In a seminal paper published in 1951, Taylor studied the interactions between a viscous fluid and an immersed flat sheet which is subjected to a travelling wave of transversal displacement. The net reaction of the fluid over the sheet turned out to be a force in the direction of the wave phase-speed. This effect is a key mechanism for the swimming of micro-organisms in viscous fluids. Here, we study the interaction between a viscous fluid and a special class of nonlinear morphing shells. We consider pre-stressed shells showing a one-dimensional set of neutrally stable equilibria with almost cylindrical configurations. Their shape can be effectively controlled through embedded active materials, generating a large-amplitude shape-wave associated with precession of the axis of maximal curvature. We show that this shape-wave constitutes the rotational analogue of a Taylor's sheet, where the translational swimming velocity is replaced by an angular velocity. Despite the net force acting on the shell vanishes, the resultant torque does not. A similar mechanism can be used to manoeuver in viscous fluids.

8.
Nat Commun ; 9(1): 938, 2018 03 05.
Article in English | MEDLINE | ID: mdl-29507295

ABSTRACT

Microtubule asters must be positioned precisely within cells. How forces generated by molecular motors such as dynein are integrated in space and time to enable such positioning remains unclear. In particular, whereas aster movements depend on the drag caused by cytoplasm viscosity, in vivo drag measurements are lacking, precluding a thorough understanding of the mechanisms governing aster positioning. Here, we investigate this fundamental question during the migration of asters and pronuclei in C. elegans zygotes, a process essential for the mixing of parental genomes. Detailed quantification of these movements using the female pronucleus as an in vivo probe establish that the drag coefficient of the male-asters complex is approximately five times that of the female pronucleus. Further analysis of embryos lacking cortical dynein, the connection between asters and male pronucleus, or the male pronucleus altogether, uncovers the balance of dynein-driven forces that accurately position microtubule asters in C. elegans zygotes.


Subject(s)
Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans/metabolism , Dyneins/metabolism , Microtubules/metabolism , Zygote/metabolism , Animals , Cell Nucleus/metabolism , Centrosome/metabolism , Cytoplasm/chemistry , Embryo, Nonmammalian/metabolism , Female , Male , Viscosity
9.
J Small Anim Pract ; 58(3): 125-138, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28267216

ABSTRACT

In order to evaluate possible nervous system involvement in canine leishmaniasis, retrospective evaluation of all medical records of leishmaniotic dogs exhibiting neurological signs referred to our hospital over a 5-year period was performed. The records of 10 dogs were reviewed. Depending on the neuroanatomical localisation, the dogs underwent advanced diagnostic imaging, cerebrospinal fluid analysis, electrodiagnostic testing and histopathologic evaluations. The final neurological diagnosis was: meningoencephalitis (n=2), brain haemorrhagic stroke (n=1), haemorrhagic choroiditis (n=1), meningomyelitis (n=2), ischaemic myelopathy (n=1), polymyositis (n=2) and peripheral neuropathy (n=1). This study confirms that both central and peripheral nervous systems can be affected by leishmaniasis and provides an overview on the possible etiopathogenetic mechanisms. In addition, clinical and diagnostic findings, therapy and follow-up of affected dogs are described.


Subject(s)
Dog Diseases/parasitology , Leishmania infantum/isolation & purification , Leishmaniasis, Visceral/veterinary , Animals , Dog Diseases/diagnosis , Dog Diseases/pathology , Dog Diseases/physiopathology , Dogs , Italy , Leishmaniasis, Visceral/diagnosis , Leishmaniasis, Visceral/pathology , Leishmaniasis, Visceral/physiopathology , Retrospective Studies
10.
J Am Coll Cardiol ; 37(6): 1639-44, 2001 May.
Article in English | MEDLINE | ID: mdl-11345378

ABSTRACT

OBJECTIVES: We tested the hypothesis that the response to flecainide infusion can identify patients with atrial fibrillation (AF) in whom the hybrid pharmacologic and ablation therapy reduces the recurrences of AF. BACKGROUND: Infusion of class IC anti-arrhythmic drugs may promote transformation of AF into atrial flutter. Catheter ablation of atrial flutter has been demonstrated to be highly effective in preventing recurrences of atrial flutter. METHODS: Seventy-one consecutive patients with paroxysmal or chronic AF, in whom flecainide infusion (2 mg/kg body weight, intravenously) determined the transformation of AF into common atrial flutter (positive response), were randomized to receive one of the following treatments: oral pharmacologic treatment with flecainide (group A, n = 23); the hybrid treatment (catheter ablation of the inferior vena cava-tricuspid annulus isthmus, plus oral flecainide) (group B, n = 24); or catheter ablation of the isthmus only (group C, n = 24). Thirty-seven patients with a negative response to flecainide, who chose to be submitted to the hybrid treatment, were selected as the control group (group D). RESULTS: During a mean follow-up period of 24 +/- 7.2 months, the recurrences of AF and atrial flutter in group B (42%) were significantly lower than those in group A (78%, p < 0.001), group C (92%, p < 0.001) and group D (92%, p < 0.001). CONCLUSIONS: The creation of a complete bi-directional conduction block at the inferior vena cava-tricuspid annulus isthmus, plus flecainide administration, reduces the recurrences of both AF and atrial flutter in patients with class IC atrial flutter. Moreover, the early response to flecainide is safe and reliable in identifying patients who may benefit from this therapy.


Subject(s)
Anti-Arrhythmia Agents/therapeutic use , Atrial Fibrillation/drug therapy , Catheter Ablation , Flecainide/therapeutic use , Administration, Oral , Aged , Analysis of Variance , Atrial Fibrillation/complications , Atrial Fibrillation/diagnosis , Atrial Flutter/etiology , Catheter Ablation/methods , Chronic Disease , Combined Modality Therapy , Disease-Free Survival , Electrocardiography , Female , Follow-Up Studies , Humans , Infusions, Intravenous , Male , Middle Aged , Patient Selection , Predictive Value of Tests , Proportional Hazards Models , Recurrence , Treatment Outcome
11.
J Am Coll Cardiol ; 27(5): 1090-7, 1996 Apr.
Article in English | MEDLINE | ID: mdl-8609326

ABSTRACT

OBJECTIVES: We compared the efficacy of two different mapping techniques in identifying the ablation site for atrial tachycardia. Moreover, we evaluated the additive positive predictive value of mechanical interruption of atrial tachycardia to reduce the number of ineffective radiofrequency applications. BACKGROUND: Radiofrequency catheter ablation has been suggested as a highly effective technique to treat drug-resistant atrial tachycardia. However, irrespective of the mapping technique utilized, success was most often achieved with a large number of radiofrequency applications. METHODS: Forty-five patients with atrial tachycardia underwent radiofrequency catheter ablation. Mapping techniques included identification of earliest atrial activation and pace-mapping concordant sequence. RESULTS: Atrial tachycardia was successfully treated in 42 (93.3%) of 45 patients with a mean of 3.9 radiofrequency pulses/patient. An interval between the onset of the intracavitary atrial deflection and the onset of the P wave during atrial tachycardia (AP interval) > or = 30 ms (p < 0.001) and pace-mapping concordant sequence (p = 0.01) were all significant predictors of outcome. An AP interval > or = 30 ms and a pace-mapping concordant sequence were highly sensitive (92.8%, 95% confidence interval [CI] 80.5% to 98.5%; 85.7%, 95% CI 71.5% to 94.6%, respectively) but less specific (47.8%, 95% CI 37.9% to 58.2%, 36.8%, 95% CI 27.6% to 47.2%, respectively) in identifying the site of ablation. By using atrial tachycardia mechanical interruption combined with the AP interval >30 ms or the pace-mapping concordant sequence, we obtained a specifically of 76.5% (95% CI 66.4% to 84.0%) and 73.5% (95% CI 63.2% to 81.4%), respectively, and a positive predictive value of 49.2% and 44.6%, respectively. CONCLUSIONS: An AP interval > or = 30 ms and a pace-mapping concordant sequence were reliable mapping features for predicting the outcome of the ablation procedure. Mechanical interruption of atrial tachycardia improved the specificity and positive predictive value of these two mapping techniques.


Subject(s)
Catheter Ablation/methods , Tachycardia, Supraventricular/surgery , Adolescent , Adult , Child , Electrocardiography , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Tachycardia, Supraventricular/physiopathology
12.
J Am Coll Cardiol ; 34(3): 810-4, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10483964

ABSTRACT

OBJECTIVES: To evaluate, in a prospective and randomized fashion, the efficacy of a pretreatment with verapamil (V) in reducing recurrences of atrial fibrillation (AF) after electrical cardioversion (C). BACKGROUND: The increased vulnerability for AF recurrence is probably due to AF-induced changes in the electrophysiologic properties of the atria. This electrical remodeling seems to be due to intracellular calcium overload. METHODS: One hundred seven patients with persistent or chronic AF underwent external and/or internal C. All patients received oral propafenone (P) (900 mg/day) three days before and during the entire period of follow-up (three months). In the first group, patients received only the P. In the second group, in adjunct to P, oral V (240 mg/day) was initiated three days before C and continued during the follow-up. Finally, in the third group, oral V was administered three days before and continued only for three days after electrical C. RESULTS: During the three months of follow-up, 23 patients (23.7%) had AF recurrence. Mantel-Haenszel cumulative chi-square reached a significant level only when comparing AF free survival curves of group I versus group II and group III (chi-square = 5.2 and 4, respectively; p < 0.05). Significantly, 15 (65.2%) AF relapses occurred during the first week after cardioversion with a higher incidence in group I (10/33 patients, 30.3%) than group II (2/34 patients, 5.9%; p = 0.01) and group III (3/30 patients, 10%; p = 0.04). CONCLUSIONS: Six days of oral V administration centered on the C day, combined with P, significantly reduce the incidence of early recurrences of AF compared with P alone.


Subject(s)
Anti-Arrhythmia Agents/therapeutic use , Atrial Fibrillation/therapy , Electric Countershock , Premedication , Verapamil/therapeutic use , Aged , Atrial Fibrillation/diagnosis , Chronic Disease , Combined Modality Therapy , Electric Countershock/methods , Electric Countershock/statistics & numerical data , Electrocardiography , Female , Humans , Male , Middle Aged , Premedication/methods , Premedication/statistics & numerical data , Propafenone/therapeutic use , Prospective Studies , Recurrence , Treatment Outcome
13.
Vet Comp Orthop Traumatol ; 28(2): 145-50, 2015.
Article in English | MEDLINE | ID: mdl-25650786

ABSTRACT

An 11-year-old intact female Doberman Pinscher was presented with the complaint of non-ambulatory tetraparesis. Clinical and neurological examination revealed a caudal cervical spinal cord disfunction (C6-T2 spinal cord segments). Magnetic resonance imaging and computed tomographic (CT) findings of the cervical spine were consistent with caudal cervical spondylomyelopathy (CSM). During the diagnostic work-up for the cervical spine, bilateral bone anomalies involving the seventh cervical vertebra and the first ribs were found on radiographs and CT examination. The rib anomalies found in this dog appear similar to cervical ribs widely described in human medicine. In people, cervical ribs are associated with a high rate of stillbirth, early childhood cancer, and can cause the thoracic outlet syndrome, characterized by neurovascular compression at level of superior aperture of the chest. In dogs, only some sporadic anatomopathological descriptions of cervical ribs exist. In this report the radiographic and CT findings of these particular vertebral and rib anomalies along with their relationships with adjacent vasculature and musculature are shown intravitam in a dog. Specific radiographic and CT findings described in this report may help in reaching a presumptive diagnosis of this anomaly. Finally, their clinical and evolutionary significance are discussed.


Subject(s)
Dogs/abnormalities , Ribs/abnormalities , Spinal Cord Diseases/veterinary , Animals , Decompression, Surgical/veterinary , Dog Diseases/diagnosis , Dog Diseases/surgery , Female , Radiography , Ribs/diagnostic imaging , Spinal Cord Diseases/diagnosis , Spinal Cord Diseases/surgery
14.
Hypertension ; 10(6): 595-602, 1987 Dec.
Article in English | MEDLINE | ID: mdl-2961689

ABSTRACT

The effects of graded lower body negative pressure (-10 and -40 mm Hg) on vascular resistance and plasma vasopressin, norepinephrine, and renin activity were assessed in seven hypertensive subjects with left ventricular hypertrophy and seven sex-matched and age-matched normotensive subjects. In both groups increasing levels of lower body negative pressure induced a progressive decrease in right atrial pressure and an increase in vascular resistance. In normal subjects plasma vasopressin, norepinephrine, and renin activity were progressively raised, whereas only the higher level of stimulation increased plasma renin activity, norepinephrine, and vasopressin in hypertensive subjects. Propranolol induced a significant increase in plasma vasopressin in normal subjects (from 1.3 +/- 0.1 to 2.0 +/- 0.1 pg/ml; p less than 0.05) but not in hypertensive subjects. In this latter condition -10 mm Hg lower body negative pressure failed to increase plasma vasopressin, norepinephrine, and renin activity in normal subjects. Propranolol abolished the change in plasma renin activity in both groups, reduced the increase in vascular resistance induced by -40 mm Hg lower body negative pressure in normotensive subjects, but did not modify the rise in vasopressin elicited by this stimulus in normal subjects or the humoral and hemodynamic reflex responses evoked in hypertensive subjects. These results suggest that cardiopulmonary receptors are involved in the control of vasopressin release in normal subjects, whereas in hypertensive subjects with left ventricular hypertrophy, this control is altered because of an impaired function of cardiopulmonary receptors.


Subject(s)
Arginine Vasopressin/metabolism , Cardiomegaly/physiopathology , Hypertension/physiopathology , Pressoreceptors/physiology , Adult , Blood Pressure , Female , Humans , Lower Body Negative Pressure , Male , Norepinephrine/metabolism , Propranolol , Reflex/physiology , Renin/metabolism , Vascular Resistance
15.
Arch Neurol ; 55(6): 854-6, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9626778

ABSTRACT

OBJECTIVE: To describe a mother and her 2 sons affected by idiopathic intracranial hypertension (IIH), associated in the sons with root irritation symptom. Unlike the other 4 families reported previously, obesity was not present in our patients. DESIGN: Case reports. SETTING: Department of pediatrics in a university school of Medicine, Naples, Italy. PATIENTS: A mother (aged 36 years) and her 2 sons (aged 14 and 9 years) developed IIH at different times. Neuroimaging showed an empty sella in the mother, while IIH was associated with spinal and radicular pain in her 2 sons. The mother and the younger son developed permanent visual loss. CONCLUSIONS: Ophthalmologic follow-up in our patients indicates that IIH is a chronic disease. Surgical treatment should be considered an option.


Subject(s)
Intracranial Hypertension/complications , Intracranial Hypertension/genetics , Pain/etiology , Polyradiculopathy/etiology , Adolescent , Adult , Child , Female , Humans , Intracranial Hypertension/diagnosis , Magnetic Resonance Imaging , Male , Sella Turcica/pathology , Spine , Vision Disorders/etiology
16.
Neuropsychologia ; 37(7): 797-805, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10408647

ABSTRACT

Alertness, the most basic intensity aspect of attention, probably is a prerequisite for the more complex and capacity demanding domains of attention selectivity. Behaviorally, intrinsic alertness represents the internal (cognitive) control of wakefulness and arousal; typical tasks to assess optimal levels of intrinsic alertness are simple reaction time measurements without preceding warning stimuli. Up until now only parts of the cerebral network subserving alertness have been revealed in animal, lesion, and functional imaging studies. Here, in a 15O-butanol PET activation study in 15 right-handed young healthy male volunteers for this basic attention function we found an extended right hemisphere network including frontal (anterior cingulate-dorsolateral cortical)-inferior parietal-thalamic (pulvinar and possibly the reticular nucleus) and brainstem (ponto-mesencephalic tegmentum, possibly involving the locus coeruleus) structures, when subjects waited for and rapidly responded to a centrally presented white dot by pressing a response key with the right-hand thumb.


Subject(s)
Attention/physiology , Brain/anatomy & histology , Brain/physiology , Signal Detection, Psychological , Adult , Analysis of Variance , Brain Stem/anatomy & histology , Brain Stem/physiology , Frontal Lobe/anatomy & histology , Frontal Lobe/physiology , Humans , Male , Nerve Net/anatomy & histology , Nerve Net/physiology , Parietal Lobe/anatomy & histology , Parietal Lobe/physiology , Reaction Time , Reference Values , Thalamus/anatomy & histology , Thalamus/physiology , Tomography, Emission-Computed , Volunteers
17.
Am J Cardiol ; 55(1): 116-21, 1985 Jan 01.
Article in English | MEDLINE | ID: mdl-3966371

ABSTRACT

Renal function and systemic hemodynamics were assessed in 10 hypertensive patients and in 10 age-matched normotensive subjects during control conditions (80 mEq of sodium/day) and after a salt load, either alone (480 mEq/day) or combined with indomethacin or sulindac. Indomethacin was used to induce ubiquitous inhibition of prostaglandin synthesis and sulindac to inhibit prostaglandin synthesis in all tissues except the kidney. Under control conditions there was no significant difference between the 2 groups in any measurement except blood pressure and total peripheral resistance. Also, the changes induced by salt load in the 2 groups were comparable. However, after indomethacin administration, only hypertensive patients showed a significant reduction in the 24-hour sodium excretion (from 417 +/- 61 to 317 +/- 49 mEq, p less than 0.05), so that the difference between this value and the corresponding value of normotensive subjects (453 +/- 79 mEq) became significant (p less than 0.05). The changes in sodium excretion in hypertensive patients were significantly correlated with the changes in renal plasma flow (r = 0.803, p less than 0.01). However, cardiac output and renal blood flow showed a similar pattern in normal and hypertensive persons. Finally, after the addition of sulindac to salt load, the differences in the 24-hour sodium excretion vanished. These results were also confirmed in an ancillary study performed, using the same protocol, in 10 other hypertensive patients using ibuprofen rather than indomethacin. Our data suggest that renal prostaglandins participate in renal disposal of chronic salt load in hypertensive patients but not in normal persons.


Subject(s)
Hypertension/physiopathology , Kidney/physiopathology , Prostaglandins/physiology , Sodium Chloride/administration & dosage , Sodium/urine , Adolescent , Adult , Blood Pressure/drug effects , Cardiac Output/drug effects , Diuresis/drug effects , Female , Humans , Hypertension/urine , Ibuprofen/pharmacology , Indomethacin/pharmacology , Male , Middle Aged , Potassium/urine , Sulindac/pharmacology , Vascular Resistance/drug effects
18.
Int J Oncol ; 18(6): 1245-9, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11351258

ABSTRACT

1-beta-D-arabinofuranosylcytosine (ara-C) is an antimetabolite used for the treatment of acute myelogenous leukemia. The ability of ara-C to kill neoplastic cells has been correlated to the induction of apoptosis. The clinical use of ara-C is limited by the development of drug resistance. Alterations in drug-induced apoptosis play a critical role in ara-C resistance. In particular, the proto-oncogene bcl-2 has been implicated in this phenomenon. To better understand the molecular basis of the role of bcl-2 in ara-C resistance, we investigated the relationship between the cytotoxic effect of ara-C, the expression levels and the subcellular localization of bcl-2 in three human leukemic cell lines (HL-60, KG1, J111). We have also evaluated the effects of ara-C on the J111 leukemic cell line (showing the lowest levels of Bcl-2 and the highest sensitivity to ara-C) overexpressing the bcl-2 oncogene. The model we developed here will allow further studies on the role of post-translational events involving bcl-2 (such as translocation and/or phosphorylation) in the cellular response to ara-C treatment.


Subject(s)
Antimetabolites, Antineoplastic/pharmacology , Cytarabine/pharmacology , HL-60 Cells/drug effects , Proto-Oncogene Proteins c-bcl-2/metabolism , Cell Survival/drug effects , DNA Fragmentation , Drug Resistance, Neoplasm , HL-60 Cells/metabolism , Humans , Isoenzymes/metabolism , Protein Kinase C/metabolism , Protein Kinase C-alpha , Proto-Oncogene Mas , Proto-Oncogene Proteins c-bcl-2/genetics , Transfection
19.
Spine (Phila Pa 1976) ; 19(9): 1087-91, 1994 May 01.
Article in English | MEDLINE | ID: mdl-8029748

ABSTRACT

STUDY DESIGN: The first clinical implementation of a microsurgical endoscopic technique for removal of thoracic disc herniation is described. OBJECTIVE: To decompress the spinal cord with a ventral approach, combining microsurgical and endoscopic techniques, while reducing the "approach-related trauma." METHODS: A detailed description of the preoperative preparation as well as the surgical technique is given. Advantages and disadvantages of the microsurgical endoscopic technique are discussed and compared with other surgical procedures described in the literature. RESULTS: A herniated disc at T6-T7 was removed and the spinal cord was decompressed. The patient recovered completely and was discharged at the seventh postoperative day. He returned to work 4 weeks later. CONCLUSIONS: The microsurgical endoscopic technique allows spinal cord decompression with a substantial reduction in surgical trauma. It may shorten bed confinement and allow early return to active life. Application of this technique in other areas is being studied.


Subject(s)
Diskectomy/methods , Intervertebral Disc Displacement/surgery , Thoracic Vertebrae/surgery , Adult , Cadaver , Endoscopy/methods , Humans , Male , Microsurgery/methods
20.
Rofo ; 161(2): 106-12, 1994 Aug.
Article in German | MEDLINE | ID: mdl-8054542

ABSTRACT

The neuroradiological studies (CT, MRI, angiography) in 21 children with perinatal HIV infection were reviewed retrospectively. No patient showed an intracranial mass lesion; after intravenous contrast medium application there was no case with disturbed blood-brain barrier. Common non-specific findings were atrophy and delayed myelination. In 7 cases atrophy was combined with multifocal nearly symmetric white matter lesions, which characteristically spared the U-fibres. Further findings included an intramedullary ring-shaped structure in the cervical cord, an AIDS-associated vasculopathy and symmetric calcifications in the basal ganglia. The spectrum of neuroradiological findings in paediatric AIDS patients differs from that in adults. Knowledge of these age-specific findings is important because the number of HIV-infected children is rising.


Subject(s)
Central Nervous System/diagnostic imaging , HIV Infections/diagnostic imaging , Age Factors , Atrophy , Basal Ganglia/pathology , Brain/pathology , Cerebral Angiography , Child , Child, Preschool , Female , HIV Infections/diagnosis , Humans , Infant , Magnetic Resonance Imaging , Male , Retrospective Studies , Spinal Cord/pathology , Tomography, X-Ray Computed
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