The Erice 58 Charter on 'The health of migrants. An equity challenge for the public health system'.

Abstract: The Erice 58 Charter titled "The Health of Migrants: a Challenge of Equity for the Public Health System", was unanimously approved at the conclusion of the 58th Residential Course of the School of Epidemiology and Preventive Medicine 'Giuseppe D'Alessandro' entitled "The Health of Migrants: a Challenge of Equity for the Public Health System. Epidemiological, clinical-relational, regulatory, organisational, training and public communication aspects at international, national and local level', which took place from 28 March to 2 April 2022 in Erice (Sicily, Italy), at the 'Ettore Majorana' Foundation and Centre for Scientific Culture. The Course was promoted by the Italian Society of Migration Medicine (S.I.M.M.) and the Italian Society of Hygiene, Preventive Medicine and Public Health (SItI), with the collaboration and patronage of the Istituto Superiore di Sanità (ISS). 72 learners participated (mainly resident doctors in 'Hygiene and Preventive Medicine' but also other health service professionals), whose average age was 37 years; on the basis of territorial origin, 13 of the 20 Italian regions were represented. During the intense learning experience, which consisted of 18 frontal lessons (with 20 lecturers from the bio-medical, socio-anthropological and journalistic fields) and 7 working group sessions (supported by 4 classroom tutors in addition to the lecturers) in 'blended learning' mode, the various dimensions and critical issues related to the possibility of guaranteeing truly inclusive health policies for foreigners/migrants, throughout the country, were identified and discussed from an 'Health Equity' perspective. This enabled a small editorial group to draw up the basic document that, in the last session of the Course, was discussed and modified by all participants into the version of the 'Erice 58 Charter' presented here.

Is the mental health profile of immigrants changing? A national-level analysis based on hospital discharges in Italy.

BACKGROUND: Among asylum seekers and refugees in European countries, several studies have shown a high burden of mental disorders, including post-traumatic stress disorder, anxiety, depression and psychoses. The present study compares hospitalization for mental disorders among migrants arriving from countries typically linked to the refugee phenomenon (putative asylum seekers), migrants arriving from other countries, and natives. METHODS: The study is based on hospital discharge data collected at the national level by the Italian Ministry of Health. Age-standardized hospitalization rates for mental health diagnoses are calculated for the three groups during the period 2008-2015. Differences in type of admission (urgent or planned) and length of stay in hospital are also assessed. RESULTS: Temporal trends show a general decrease of hospitalization rates for mental disorders among both immigrants and natives; however, an increase is observed among young male putative asylum seekers (from 30.3 in 2010 to 43.6 per 10,000 in 2015), mainly due to admissions for "other nonorganic psychoses". CONCLUSION: These findings suggest that in Italy a higher burden of mental disorders might derive from the landing phenomenon, and the increase of hospitalization ascribed to "other nonorganic psychoses" (which is a general and unspecific diagnostic label) might conceal diagnostic difficulties by Italian psychiatrists to recognize atypical pictures associated with traumatic experiences.

HrQoL in hair loss-affected patients with alopecia areata, androgenetic alopecia and telogen effluvium: the role of personality traits and psychosocial anxiety.

BACKGROUND: Illness impact on HrQoL has been widely studied in hair loss-affected patients, yet no study has addressed whether individual differences modulate HrQoL in patients with alopecia areata (AA), androgenetic alopecia (AGA) and telogen effluvium (TE). OBJECTIVE: To identify the personality dimensions most predictive of the impact of disease on HrQoL. METHOD: A single-site cross-sectional study was carried out in the Dermatology Unit of Sant'Orsola-Malpighi Hospital, Bologna between September 2016 and September 2017. The study included 143 patients (105 females, ages 18-60 years) diagnosed with AA (n = 27), AGA (n = 80) and TE (n = 36). Illness severity, alopecia type, age, gender, education and civil status were documented. Health-related quality of life (HrQoL), personality traits, trait anxiety, emotional intelligence, social anxiety and social phobia were also measured. RESULTS: AA, AGA and TE groups differed significantly for illness severity with most severe patients falling in AA type. For HrQoL, Gender × Group interaction resulted significant with AGA females reporting a higher impact of hair loss on quality of life than males, while TE males were more impacted by hair loss than AA and AGA males. Lower scores were obtained by AGA females than males on emotional intelligence while no significant differences were evidenced on other groups. A significant Gender × Group interaction was also found for trait anxiety, social phobia and social anxiety: consistently, AGA females reported higher scores than AGA males in all three measures. Finally, discriminant analysis evidenced that anxiety-related traits can contribute to reliably predict hair loss impact on HrQoL, regardless of illness severity and alopecia type. CONCLUSIONS: We recommend that gender and individual differences in anxiety-related dimensions be considered as key factors in gaining a deeper understanding of hair loss impact on quality of life as well as in reducing the burden of illness in alopecia-affected patients.

Plastic reorganization of neural systems for perception of others in the congenitally blind.

Recent evidence suggests that the function of the core system for face perception might extend beyond visual face-perception to a broader role in person perception. To critically test the broader role of core face-system in person perception, we examined the role of the core system during the perception of others in 7 congenitally blind individuals and 15 sighted subjects by measuring their neural responses using fMRI while they listened to voices and performed identity and emotion recognition tasks. We hypothesised that in people who have had no visual experience of faces, core face-system areas may assume a role in the perception of others via voices. Results showed that emotions conveyed by voices can be decoded in homologues of the core face system only in the blind. Moreover, there was a specific enhancement of response to verbal as compared to non-verbal stimuli in bilateral fusiform face areas and the right posterior superior temporal sulcus showing that the core system also assumes some language-related functions in the blind. These results indicate that, in individuals with no history of visual experience, areas of the core system for face perception may assume a role in aspects of voice perception that are relevant to social cognition and perception of others' emotions.

Age-related differences in sleep-dependent consolidation of motor skills in patients with narcolepsy type 1.

OBJECTIVE: The influence of post-training sleep on the consolidation process of procedural (ie, visual and motor) knowledge has shown to be less effective in patients with chronic sleep disorders compared with healthy subjects. To ascertain whether the influence of the altered architecture of sleep in patients with narcolepsy type 1 (ie, with cataplexy: NT1) also varies with age, we compared the performance values of 16 children (aged from nine to 14 years) and 16 adults (aged from 24 to 51 years) on finger tapping task (FTT) after daytime and nighttime periods of sleep in the 24 hours following training. METHODS: All patients, who were drug-free and underwent continuous polysomnographic recordings, could take one or more naps after the training session (at 10 a.m.) until one hour before the first retrieval session (at 6 p.m.) and had an undisturbed period of nighttime sleep from about 10 p.m. to two hours before the second retrieval session (again at 10 a.m.). RESULTS: The pattern of sleep-dependent consolidation was significantly different in the two groups of patients: while performance accuracy was higher in adults compared with children at each session, performance speed improved after daytime sleep in children and after nighttime sleep in adults. The improvement in performance speed, although not related with any sleep parameters in both groups, was positively correlated with the daytime and nighttime total sleep time (TST) in children with greater consolidation gain. CONCLUSION: The interaction between time of day and age in the time course of consolidation of new motor skills discloses a different role of daytime sleep (active in children, simply protective from interferences in adults) in NT1 patients and suggests a flexible use of napping in the educational context.

Sleep-dependent consolidation of motor skills in patients with narcolepsy-cataplexy.

BACKGROUND AND OBJECTIVES: This study investigated whether the altered organization of post-training sleep in patients with narcolepsy-cataplexy (NC) is associated with a lower off-line improvement in the consolidation of motor skills compared with normal subjects. STUDY DESIGN: Fourteen drug-naive NC patients, fulfilling the international clinical and polysomnographic diagnostic criteria, and 14 individually-matched controls underwent training at a sequential finger tapping task (FTT) and were re-tested on the next morning (after a night with polysomnographic recording) and after another six nights (spent at home). SETTING: Training and retrieval sessions were performed in a controlled laboratory setting. RESULTS: FTT performance was worse in NC patients than controls at training and at both retrieval sessions and showed a fairly different time course (slower than in controls) of consolidation. Several sleep indices (lower values of stage-2 NREM sleep and SWS) were compatible with a lower effectiveness of sleep for consolidation of motor skills in NC patients, although no statistically significant relationship was found between such indices and improvement rate. CONCLUSION: The consolidation process of motor skills results less effective in NC patients since training and slower than in normal subjects over the week following training. The wider variations in performance scores and sleep parameters of post.-training night in NC patients relative to controls suggest that a) the lower initial consolidation may be due to a less effective encoding consequent to altered prior sleep, and b) the consolidation process over the 24 h following training is negatively influenced not only by the altered characteristics of post-training sleep, but also by the daytime sleepiness following training.

Hepatic 11 beta-hydroxysteroid dehydrogenase 1 involvement in alterations of glucose metabolism produced by acidotic stress in rat

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11 beta-hydroxysteroid dehydrogenase (HSDs) enzymes regulate the activity of glucocorticoids in target organs. HSD1, one of the two existing isoforms, locates mainly in CNS, liver and adipose tissue. HSD1 is involved in the pathogenesis of diseases such as obesity, insulin resistance, arterial hypertension and the Metabolic Syndrome. The stress produced by HCl overload triggers metabolic acidosis and increases liver HSD1 activity associated with increased phosphoenolpyruvate carboxykinase, a regulatory enzyme of gluconeogenesis that is activated by glucocorticoids, with increased glycaemia and glycogen breakdown. The aim of this study was to analyze whether the metabolic modifications triggered by HCl stress are due to increased liver HSD1 activity. Glycyrrhetinic acid, a potent HDS inhibitor, was administered subcutaneously (20 mg/ml) to stressed and unstressed four months old maleSprague Dawley rats to investigate changes in liver HSD1, phosphoenolpyruvate carboxykinase (PECPK) and glycogen phosphorylase activities and plasma glucose levels. It was observed that all these parameters increased in stressed animals, but that treatment with glycyrrhetinic acid significantly reduced their levels. In conclusion, our results demonstrate the involvement of HSD1 in stress induced carbohydrate disturbances and could contribute to the impact of HSD1 inhibitors on carbohydrate metabolism and its relevance in the study of Metabolic Syndrome Disorder and non insulin-dependent diabetes mellitus (AU)

Hepatic 11 beta-hydroxysteroid dehydrogenase 1 involvement in alterations of glucose metabolism produced by acidotic stress in rat.

11 beta-hydroxysteroid dehydrogenase (HSDs) enzymes regulate the activity of glucocorticoids in target organs. HSD1, one of the two existing isoforms, locates mainly in CNS, liver and adipose tissue. HSD1 is involved in the pathogenesis of diseases such as obesity, insulin resistance, arterial hypertension and the Metabolic Syndrome. The stress produced by HCl overload triggers metabolic acidosis and increases liver HSD1 activity associated with increased phosphoenolpyruvate carboxykinase, a regulatory enzyme of gluconeogenesis that is activated by glucocorticoids, with increased glycaemia and glycogen breakdown. The aim of this study was to analyze whether the metabolic modifications triggered by HCl stress are due to increased liver HSD1 activity. Glycyrrhetinic acid, a potent HDS inhibitor, was administered subcutaneously (20 mg/ml) to stressed and unstressed four months old maleSprague Dawley rats to investigate changes in liver HSD1, phosphoenolpyruvate carboxykinase (PECPK) and glycogen phosphorylase activities and plasma glucose levels. It was observed that all these parameters increased in stressed animals, but that treatment with glycyrrhetinic acid significantly reduced their levels. In conclusion, our results demonstrate the involvement of HSD1 in stress induced carbohydrate disturbances and could contribute to the impact of HSD1 inhibitors on carbohydrate metabolism and its relevance in the study of Metabolic Syndrome Disorder and non insulin-dependent diabetes mellitus.

Central and cardiovascular responses to emotional stimuli are normal in non-phobic subjects with Reflex Syncope.

OBJECTIVE: Reflex Syncope (RS) is a self-limited loss of consciousness due to systemic arterial hypotension resulting from widespread vasodilatation and/or bradycardia. Higher neural centres have been implicated in the pathophysiology of RS, particularly in blood/injury phobic patients. We investigated interictal central autonomic functions in non-phobic RS subjects compared to non-phobic controls evaluating their central and cardiovascular responses to emotional stimuli. METHODS: Cardiovascular responses to Valsalva Manoeuvre (VM), Deep Breathing (DB) and during presentation of 108 slides selected from the International Affective Picture System were assessed in 20 non-phobic RS subjects and 20 controls. Slide onset visual event-related potentials (ERPs) were also computed. RESULTS: No significant difference in cardiovascular responses and ERP amplitude were found in non-phobic RS subjects and controls at rest, in response to VM and DB or during picture presentation. CONCLUSIONS: Non-phobic patients with RS not only have a normal interictal autonomic control of the cardiovascular system but also a normal modulation and adaptation of central and cardiovascular response to emotional processing, in our experimental setting. SIGNIFICANCE: Non-phobic patients with RS present normal interictal central and cardiovascular responses. Autonomic dysfunction observed in phobic RS patients could be related to mechanisms underlying the phobia itself rather than the mechanisms causing RS.

[Experimental formative tools for the personnel and organizing models for a Nuclear Medicine Service of the public healthcare in Italy]. / Modelli sperimentali di formazione del personale ed organizzazione del lavoro in un Servizio di Medicina Nucleare Pubblica in Italia.

In the present prospective study started in 2004, we evaluated the potential role of the ''job on site'' model as a formative tool previously proposed by the ''Ministero della Salute'' in Italy and at the moment it is yet in an experimental phase in our Country. We applied this ''job on site'' model for the development of a new Nuclear Medicine Service in Rovigo Hospital (ULSS 18 of Veneto Region Italy). Moreover, there were planned, experimented and applied different organizing working models involving both physicians, technicians and nurses. The indicators of productivity realised in the period August 2004 to June 2007 were taken as end points. In our experience, the ''job on site'' model was particularly useful as a formative tool, and allowed a qualified preparation of the Service personnel as well as a rapid achievement of standard Regional and National indicators of productivity. Moreover, from a cost-effectiveness point of view, the daily working model we applied, that is based on a prolongation of the daily work per operator, proved to be highly effective in our Hospital. The data reported here may be of interest for the future planning of similar Services in the Public National and Regional Healthcare.

Clinical features, diagnostic and therapeutic approaches to haematogenous vertebral osteomyelitis.

This article review the clinical features and the diagnostic approach to haematogenous vertebral osteomyelitis in order to optimise treatment strategies and follow-up assessment. Haematogenous spread is considered to be the most important route: the lumbar spine is the most common site of involvement for pyogenic infection and the thoracic spine for tuberculosis infection. The risk factors for developing haematogenous vertebral osteomyelitis are different among old people, adults and children: the literature reports that the incidence seems to be increasing in older patients. The source of infection in the elderly has been related to the use of intravenous access devices and the asymptomatic urinary infections. In young patients the increase has been correlated with the growing number of intravenous drug abusers, with endocarditis and with immigrants from areas where tuberculosis is still endemic. The onset of symptoms is typically insidious with neck or back pain often underestimated by the patient. Fever is present in 10-45% of patients. Spinal infections may cause severe neurological compromise in few cases, but mild neurological deficit, limited to one or two nerve roots, was detected in 28-35% of patients. The diagnosis of haematogenous vertebral osteomyelitis may be very difficult, as the symptoms can be sometimes not specific, vague or almost absent. The usual delay in diagnosis has been reported to be two to four months, despite the use of imaging techniques: in the early diagnosis of vertebral ostemyelitis is important the role of bone scintigraphy. The general principles for the management of spine infections are non operative, consisting of external immobilization and intravenous antibiotics, followed by oral antibiotics. Indications for surgery should be given in case of absence of clinical improvement after 2-3 weeks of intravenous antibiotics, persistent back pain and systemic effects of chronic infection and with presence or progression of neurological deficit in elderly or in cervical infection. Chronic ostemyelitis may require surgery in case of a development of biomechanical instability and/or a vertebral collapse with progressive deformity.

Determination of 1-phenylazo-2-naphthol (Sudan I) in chilli powder and in chilli-containing food products by GPC clean-up and HPLC with LC/MS confirmation.

A simple and rapid method is reported for the routine determination 1-phenylazo-2-naphthol (Sudan I) in chilli powder and in chilli-containing food products. The method involved Soxtec extraction from the products followed by high-pressure gel permeation chromatographic clean-up collecting the appropriate fraction. Analysis of this fraction was by HPLC with UV/VIS detection. The limit of detection was 7 microg kg(-1) and the limit of quantification was 13 microg kg(-1). The identity of Sudan I in food products was established by electrospray LC/MS with MS/MS confirmation. From a small survey of 30 retail samples, 11 samples of crushed chilli, Italian pasta, chilli-snack and vegetable sauce contained levels of Sudan I ranging from 24 to 5591 microg kg(-1).

Invasive Aspergillosis in Italian AIDS patients.

BACKGROUND: We studied the prevalence, epidemiological features, symptoms, diagnosis, treatment and outcome of invasive aspergillosis in AIDS patients in Italy. PATIENTS AND METHODS: All patients affected by both aspergillosis and AIDS hospitalized between January 1986 and April 1997 (before highly-active antiretroviral therapy, HAART) in four Italian Department of Infectious Disease. Patients were included in the study only if culture, cytology or histology showed firm evidence of Aspergillus infection. Invasive aspergillosis was defined as the presence of characteristic, closely septate hyphae with repeated acute angle branching in either biopsy materials or percutaneous aspirates from tissues other than the lung. Hyphae were identified using hematoxylin-eosin and methenamine silver stain. RESULTS: During the study, 54 out of 2,614 patients admitted with AIDS showed aspergillosis (2.1%). The disease usually occurred in patients with < 50 CD4 cells/mm(3). Aspergillosis was associated with neutropenia and steroid treatment. Nonspecific symptoms were frequently encountered. Fever and cough were both present in > 70% of the cases of pulmonary aspergillosis. Biopsy specimens were analyzed for definitive diagnosis. Invasive aspergillosis is usually treated with amphotericin B, but in 90% of the cases this did not prevent death. CONCLUSION: In AIDS patients with neutropenia and long-term steroid therapy, it is important to consider invasive aspergillosis in the differential diagnosis of opportunistic infections.

The decrease in uroporphyrinogen decarboxylase activity induced by ethanol predisposes rats to the development of porphyria and accelerates xenobiotic-triggered porphyria, regardless of hepatic damage.

We evaluated the porphyrinogenic ability of ethanol (20% in drinking water) per se, its effect on the development of sporadic porphyria cutanea tarda induced by hexachlorobenzene in female Wistar rats (170-190 g, N = 8/group), and the relationship with hepatic damage. Twenty-five percent of the animals receiving ethanol increased up to 14-, 25-, and 4.5-fold the urinary excretion of delta-aminolevulinate, porphobilinogen, and porphyrins, respectively. Ethanol exacerbated the precursor excretions elicited by hexachlorobenzene. Hepatic porphyrin levels increased by hexachlorobenzene treatment, while this parameter only increased (up to 90-fold) in some of the animals that received ethanol alone. Ethanol reduced the activities of uroporphyrinogen decarboxylase, delta-aminolevulinate dehydrase and ferrochelatase. In the ethanol group, many of the animals showed a 30% decrease in uroporphyrinogen activity; in the ethanol + hexachlorobenzene group, this decrease occurred before the one caused by hexachlorobenzene alone. Ethanol exacerbated the effects of hexachlorobenzene, among others, on the rate-limiting enzyme delta-aminolevulinate synthetase. The plasma activities of enzymes that are markers of hepatic damage were similar in all drug-treated groups. These results indicate that 1) ethanol exacerbates the biochemical manifestation of sporadic hexachlorobenzene-induced porphyria cutanea tarda; 2) ethanol per se affects several enzymatic and excretion parameters of the heme metabolic pathway; 3) since not all the animals were affected to the same extent, ethanol seems to be a porphyrinogenic agent only when there is a predisposition, and 4) hepatic damage showed no correlation with the development of porphyria cutanea tarda.

The decrease in uroporphyrinogen decarboxylase activity induced by ethanol predisposes rats to the development of porphyria and accelerates xenobiotic-triggered porphyria, regardless of hepatic damage

We evaluated the porphyrinogenic ability of ethanol (20 percent in drinking water) per se, its effect on the development of sporadic porphyria cutanea tarda induced by hexachlorobenzene in female Wistar rats (170-190 g, N = 8/group), and the relationship with hepatic damage. Twenty-five percent of the animals receiving ethanol increased up to 14-, 25-, and 4.5-fold the urinary excretion of delta-aminolevulinate, porphobilinogen, and porphyrins, respectively. Ethanol exacerbated the precursor excretions elicited by hexachlorobenzene. Hepatic porphyrin levels increased by hexachlorobenzene treatment, while this parameter only increased (up to 90-fold) in some of the animals that received ethanol alone. Ethanol reduced the activities of uroporphyrinogen decarboxylase, delta-aminolevulinate dehydrase and ferrochelatase. In the ethanol group, many of the animals showed a 30 percent decrease in uroporphyrinogen activity; in the ethanol + hexachlorobenzene group, this decrease occurred before the one caused by hexachlorobenzene alone. Ethanol exacerbated the effects of hexachlorobenzene, among others, on the rate-limiting enzyme delta-aminolevulinate synthetase. The plasma activities of enzymes that are markers of hepatic damage were similar in all drug-treated groups. These results indicate that 1) ethanol exacerbates the biochemical manifestation of sporadic hexachlorobenzene-induced porphyria cutanea tarda; 2) ethanol per se affects several enzymatic and excretion parameters of the heme metabolic pathway; 3) since not all the animals were affected to the same extent, ethanol seems to be a porphyrinogenic agent only when there is a predisposition, and 4) hepatic damage showed no correlation with the development of porphyria cutanea tarda

Autonomic reactivity during viewing of an unpleasant film.

The effect of an aversive, high-arousing film on heart rate, respiratory sinus arrhythmia, and electrogastrographic activity (EGG) was investigated. Previous studies have indicated a larger heart-rate deceleration for visual stimuli depicting surgery or blood compared to neutral content, and this phenomenon is similar to the bradycardia observed in animals in response to fear. The heart-rate deceleration is clearly parasympathetically driven, and it is considered a general index of attention. An accurate index of cardiac vagal tone can be obtained by means of quantification of the amplitude of respiratory sinus arrhythmia. The relationship between cardiac vagal tone and EGG is complex, but animal research has shown that suppressing vagal activity dampens gastric motility. We have investigated whether a movie depicting surgery is associated with greater heart-rate deceleration, larger increase in respiratory sinus arrhythmia, and greater increase in EGG activity compared to a neutral movie. In addition, if both respiratory sinus arrhythmia and EGG are indices of vagal tone, a positive correlation between these physiological responses was expected. Analysis indicated an effect of the surgery movie on heart rate and respiratory sinus arrhythmia, but not on EGG activity. Moreover, the expected correlation was not found. Implications for future studies are discussed.

Function and structure of rat hepatic coproporphyrinogen oxidase.

Rat hepatic coproporphyrinogen oxidase, the sixth enzyme in the heme biosynthetic pathway, was purified 1340-fold with a yield of 39.7%. To obtain the soluble enzyme, different methods were applied to disrupt mitochondria, with sonication giving the highest yield (85%). The minimum catalytic form of enzyme was a dimer with a molecular mass of 77 +/- 4 kDa. The existence of aggregated forms was possible since in fractions of gel filtration elution activity was observed with higher molecular mass. We determined a Stokes radius of 36.3 A, a sedimentation coefficient (S20,w) of 5.06 S, and frictional ratio of 1.29, suggesting a nearly globular shape of the protein. Regardless of the type of salt, high ionic strength inhibits the enzyme, probably modifying its native structure. Experiments with amino acid modifiers showed that histidine, arginine, and tryptophan are involved in the catalytic process. Non-ionic detergents and phospholipids activated the enzyme, probably because they reproduce its natural hydrophobic environment. The present study describes a simple method for the purification of rat liver coproporphyrinogen oxidase, introducing for the first time data on the structure and function of the protein in a tissue often used as a laboratory model in biological studies, and contributing to the study of human hereditary coproporphyria.

Enhanced expression of the CXCR4 co-receptor in HIV-1-infected individuals correlates with the emergence of syncytia-inducing strains.

The aim of this study was to investigate the mechanisms responsible for the emergence in some HIV-1-infected individuals of highly aggressive, syncytia-inducing (SI) HIV-1 strains, which have been shown to use CXCR4 as co-receptor to enter target cells. To this end, the percentages of circulating CXCR4+CD4+ T cells were evaluated by flow cytometry in 39 untreated and 61 highly active antiretroviral therapy (HAART)-treated HIV-1-infected individuals in comparison with 35 HIV-1 seronegative subjects. Plasma viremia was also measured, and HIV primary isolates, from both untreated and HAART-treated HIV-1-infected subjects, were tested for the presence of SI strains. The results of this study showed enhanced proportions of CXCR4+CD4+ T cells in untreated patients in comparison with HAART-treated and healthy subjects. Furthermore, the results of a 12-month longitudinal study in a cohort of 11 patients undergoing HAART showed a significant reduction of CXCR4 expression after successful therapy. Finally, a significant positive correlation among the proportions of circulating CXCR4-expressing CD4+ T cells, plasma viremia, and the probability to isolate SI strains was found. These in vivo data are in keeping with previous in vitro results suggesting a bidirectional link between HIV-1 and CXCR4 expression on CD4+ T cells, and provide some clues to understanding the mechanisms exerting a selective pressure toward the emergence of SI strains.

Simple and rapid method for the determination of coproporphyrinogen oxidase activity.

Coproporphyrinogen oxidase, the sixth enzyme in the biosynthetic heme pathway, catalyzes the oxidative decarboxylation of coproporphyrinogen III to protoporphyrinogen IX. A reversed-phase high pressure liquid chromatography method was developed to measure coproporphyrinogen oxidase enzymatic activity in rat liver. With this method, the separation, identification and quantification of coproporphyrin III (oxidized substrate) and protoporphyrin IX (oxidized product) present in the assays could be carried out with no need of derivatization and in less than 15 min. Rat and human liver coproporphyrinogen oxidase basal activities determined using this method were 0.41+/-0.05 nmol of protoporphyrin IX/h per mg of hepatic protein and 0.87+/-0.06 protoporphyrin IX/h per mg of hepatic protein, respectively. Kinetic studies showed that optimum pH for rat CPGox is 7.3, and that its activity is linear in the range of protein concentrations and incubation times assayed. The present paper describes a sensitive, specific and rapid fluorometric high performance liquid chromatography method to measure coproporphyrinogen oxidase, which could be applied to the diagnosis of human coproporphyria, and which is also suitable for the study of lead and other metal poisoning that produce alterations in this enzymatic activity.