Steroid hormones in systemic sclerosis: associations with disease characteristics and modifications during scleroderma renal crisis.

OBJECTIVE: The renin-angiotensin-aldosterone system (RAAS) and glucocorticoids (GCs) are involved in vascular remodeling and fibrosis, but have not been extensively studied in systemic sclerosis (SSc). Our aim was to investigate the RAAS and GC hormones in SSc patients. METHODS: Serum levels of renin (dosage and activity), aldosterone and its precursors (DOC, B, 18-OH-DOC, 18-OH-B), and GCs (cortisol, cortisone, 11-deoxycortisol, 18-OH-F) were assessed in 122 SSc patients and 52 healthy controls. After applying stringent inclusion criteria aimed at ensuring accurate hormone assessments (exclusion of interfering drugs, strict sampling conditions), we analyzed RAAS hormones in 61 patients, and GCs in 96 patients. Hormone levels were compared between patients and controls; and associations with disease characteristics were assessed in patients. RESULTS: Regarding RAAS hormones, SSc patients displayed significantly lower aldosterone levels (although within normal range), similar renin levels, and higher B levels than controls. Abnormal RAAS hormone levels were associated with a more severe SSc phenotype (lung and skin fibrosis, heart and pulmonary vascular involvements, inflammation). Regarding GC hormones, SSc patients had higher levels of cortisol, 11-desoxycortisol (precursor) and 18-OH-F (metabolite) but lower levels of cortisone (inactive counterpart) than controls.RAAS hormone levels were assessed in 5 SSc patients before and during scleroderma renal crisis (SRC): concentrations varied considerably between patients, but consistently included normal/increased aldosterone levels and elevated renin levels. CONCLUSION: RAAS and GC hormones are abnormally produced in SSc patients, especially in patients with severe SSc and during SRC. This could suggest a participation of these hormonal systems in SSc pathogenesis.

Indication for molecular testing by multiplex ligation-dependent probe amplification in parkinsonism.

BACKGROUND AND PURPOSE: The monogenic forms of Parkinson's disease represent <10% of familial cases and a still lower frequency of sporadic cases. However, guidelines to orient genetic testing are lacking. The aim was to establish the interest of multiplex ligation-dependent probe amplification (MLPA) as a primary screening test and to propose clinical criteria to guide genetic diagnostic tests for patients with suspected Mendelian Parkinson's disease. METHODS: In all, 567 patients with parkinsonism from 547 unrelated families were recruited and two MLPAs were performed for each. All pathogenic G2019S variants in the LRRK2 gene were confirmed by Sanger sequencing and the PRKN gene was screened for a second mutation in the cases of one heterozygous structural variant in the PRKN gene. RESULTS: The performance of MLPA was 51/567 (9%) for the entire cohort and included 27 (4.8%) LRRK2 G2019S mutations, 19 (3.4%) PRKN mutations and five (0.9%) SNCA locus duplications. The variables significantly associated with a positive test in the total cohort were North African ancestry (p < 0.0001), female sex (p = 0.004) and younger age at onset (p < 0.0008). CONCLUSIONS: Retrospective analysis allowed us to refine our indication criteria: (i) North African ancestry, (ii) an age at onset <40 years or (iii) a familial history of parkinsonism with at least one affected first-degree relative. Our study highlights the interest of MLPA testing for other parkinsonism cases with a family history, especially for patients with dementia with Lewy bodies or a multiple-system-atrophy-like phenotype.

How PrEP users constitute a community in the MSM population through their specific experience and management of stigmatization. The example of the French ANRS-PREVENIR study.

The ANRS-PREVENIR (2017-2020) prospective cohort study aims to reduce the number of new HIV infections in the "Ile-de-France" region in France, by enrolling individuals at high risk of HIV infection and proposing daily and on-demand pre-exposure prophylaxis (PrEP). The qualitative component of the ANRS-PREVENIR study aimed to investigate social and relational evolutions associated with PrEP use in men who have sex with men (MSM). In 2018, 12 focus groups with MSM (n = 68) were conducted by a social sciences researcher in Paris. A thematic analysis was performed. Results showed that stigma concerning PrEP use is a complex issue, with various kinds of stigmatization being practiced, sometimes even by the wider MSM population and PrEP users themselves. All types of stigma identified were expressed in forms of verbal abuse which made PrEP use taboo. Inside the wider MSM population a PrEP-user "community" was identified which shared a certain complicity in terms of values and a positive attitude towards PrEP. The emergence of new intragroup and intergroup social norms should be taken into account by policy makers to promote a more positive image of PrEP users.

Hip fractures and characteristics of living area: a fine-scale spatial analysis in France.

We investigated the association between hip fracture incidence and living area characteristics in France. The spatial distribution of hip fracture incidence was heterogeneous and there was a significant relationship between social deprivation, urbanization, health access, and hip fracture risk. INTRODUCTION: Several studies have shown great disparities in spatial repartition of hip fractures (HF). The aim of the study was to analyze the association between HF incidence and characteristics of the living area. METHODS: All patients aged 50 or older, living in France, who were hospitalized for HF between 2012 and 2014 were included, using the French national hospital discharge database. Standardized incidence ratio (SIR) was calculated for each spatial unit and adjusted on age and sex. An ecological regression was performed to analyze the association between HF standardized incidence and ecological variables. We adjusted the model for neighborhood spatial structure. We used three variables to characterize the living areas: a deprivation index (French-EDI); healthcare access (French standardized index); land use (percentage of artificialized surfaces). RESULTS: A total of 236,328 HF were recorded in the French hospital national database, leading to an annual HF incidence of 333/100,000. The spatial analysis revealed geographical variations of HF incidence with SIR varying from 0.67 (0.52; 0.85) to 1.45 (1.23; 1.70). There was a significant association between HF incidence rates and (1) French-EDI (trend p = 0.0023); (2) general practitioner and nurse accessibility (trend p = 0.0232 and p = 0.0129, respectively); (3) percentage of artificialized surfaces (p < 0.0001). CONCLUSION: The characteristics of the living area are associated with significant differences in the risk of hip fracture of older people.

Use of automated fetal heart rate analysis to identify risk factors for umbilical cord acidosis at birth.

OBJECTIVE: To identify clinical parameters and intrapartum fetal heart rate parameters associated with a risk of umbilical cord acidosis at birth, using an automated analysis method based on empirical mode decomposition. METHODS: Our single-center study included 381 cases (arterial cord blood pH at birth pHa ≤7.15) and 1860 controls (pHa ≥7.25) extracted from a database comprising 8,383 full datasets for over-18 mothers after vaginal or caesarean non-twin, non-breech deliveries at term (>37 weeks of amenorrhea). The analysis of a 120-min period of the FHR recording (before maternal pushing or the decision to perform a caesarean section during labor) led to the extraction of morphological, frequency-related, and long- and short-term heart rate variability variables. After univariate analyses, sparse partial least square selection and logistic regression were applied. RESULTS: Several clinical factors were predictive of fetal acidosis in a multivariate analysis: nulliparity (odds ratio (OR) 95% confidence interval (CI)]: 1.769 [1.362-2.300]), a male fetus (1.408 [1.097-1.811]), and the term of the pregnancy (1.333 [1.189-1.497]). The risk of acidosis increased with the time interval between the end of the FHR recording and the delivery (OR [95%CI] for a 1-min increment: 1.022 [1.012-1.031]). The risk factors related to the FHR signal were mainly the difference between the mean baseline and the mean FHR (OR [95%CI]: 1.292 [1.174-1.424]), the baseline range (1.027 [1.014-1.040]), fetal bradycardia (1.038 [1.003-1.075]) and the late deceleration area (1.002 [1.000-1.005]). The area under the curve for the multivariate model was 0.79 [0.76; 0.81]. CONCLUSION: In addition to clinical predictors, the automated FHR analysis highlighted other significant predictors, such as the baseline range, the instability of the FHR signal and the late deceleration area. This study further extends the routine application of automated FHR analysis during labor and, ultimately, contributes to the development of predictive scores for fetal acidosis.

Population-based incidence of lymphomas in the French Nord-Pas-de-Calais region between 2001 and 2005: Annual estimations and spatial analysis.

BACKGROUND: Non-Hodgkin's lymphomas (NHL) are the seventh most commonly diagnosed cancer in France. Nord-Pas-de-Calais is ranked as the region with the highest incidence of cancers and deaths by cancer in France. With its rich industrial past and its contrasted population densities between urban and rural territories, Nord-Pas-de-Calais represents a geographic area of interest to study the overall incidence of NHL and examine spatial variation of NHL incidence between the 170 cantons of the region. METHODS: LYMPHONOR was a population-based multicentre retrospective study of patients residing in the Nord-Pas-de-Calais region and diagnosed with NHL between January 2001 and December 2005. Spatial distribution of NHL incidence in Nord-Pas-de-Calais was explored using two complementary approaches: adjusted smoothed standardised incidence ratio (SIR) and spatial scan statistics (detection of atypical clusters). RESULTS: Between 2001 and 2005, 2132 new cases of NHL were diagnosed in the Nord-Pas-de-Calais region. In 2005, age-standardised NHL incidence rates were 10.2 and 7.0 cases per 100,000 person-years in male and female residents, respectively. No significant spatial disparities in NHL incidence were found within the Nord-Pas-de-Calais region. The age-adjusted smoothed SIR varied from 0.82 to 1.25 between cantons. Consistently, spatial scan statistics did not detect any significant atypical cluster of high NHL incidence. CONCLUSION: Comparison with national data collected during the same period does not show an overincidence of NHL in the Nord-Pas-de-Calais region. In addition, no evidence for spatial heterogeneity and clustering of NHL incidence was found within this region. Future epidemiological research using large-scale registries is needed to better appraise spatial variation of NHL incidence in France and to investigate possible reasons for significant clusters.

A generic method for improving the spatial interoperability of medical and ecological databases.

BACKGROUND: The availability of big data in healthcare and the intensive development of data reuse and georeferencing have opened up perspectives for health spatial analysis. However, fine-scale spatial studies of ecological and medical databases are limited by the change of support problem and thus a lack of spatial unit interoperability. The use of spatial disaggregation methods to solve this problem introduces errors into the spatial estimations. Here, we present a generic, two-step method for merging medical and ecological databases that avoids the use of spatial disaggregation methods, while maximizing the spatial resolution. METHODS: Firstly, a mapping table is created after one or more transition matrices have been defined. The latter link the spatial units of the original databases to the spatial units of the final database. Secondly, the mapping table is validated by (1) comparing the covariates contained in the two original databases, and (2) checking the spatial validity with a spatial continuity criterion and a spatial resolution index. RESULTS: We used our novel method to merge a medical database (the French national diagnosis-related group database, containing 5644 spatial units) with an ecological database (produced by the French National Institute of Statistics and Economic Studies, and containing with 36,594 spatial units). The mapping table yielded 5632 final spatial units. The mapping table's validity was evaluated by comparing the number of births in the medical database and the ecological databases in each final spatial unit. The median [interquartile range] relative difference was 2.3% [0; 5.7]. The spatial continuity criterion was low (2.4%), and the spatial resolution index was greater than for most French administrative areas. CONCLUSIONS: Our innovative approach improves interoperability between medical and ecological databases and facilitates fine-scale spatial analyses. We have shown that disaggregation models and large aggregation techniques are not necessarily the best ways to tackle the change of support problem.

Clinical characteristics and prognostic factors of plasmablastic lymphoma patients: analysis of 135 patients from the LYSA group.

Background: Plasmablastic lymphoma (PBL), initially described in 1997 in the oral cavity of HIV positive patients, is now recognized as a distinct aggressive and rare entity of diffuse large B-cells lymphoma by the World Health Organization (WHO) classification. Since the original description, others cases have been reported. However, these are largely derived from case reports or small series limiting any definitive conclusions on clinical characteristics and outcome. Patients and methods: The clinical, biological, pathological features and outcome of a cohort including 135 patients with PBL, from LYSA centers in France and Belgium, were reported and analyzed. Results: The median age was 58 years, with a male predominance. The cohort was divided into 56 HIV-positive patients, 17 post-transplant patients and 62 HIV-negative/non-transplanted patients. Within HIV-negative/non-transplanted, a relative immunosuppression was found in most cases (systemic inflammatory disease, history of cancer, increased age associated with weakened immune system). We have also described a new subtype, PBL arising in a chronic localized inflammatory site, without any sign of immunosuppression. At presentation, 19% of patients showed oral involvement. Immunophenotype showed CD138 positivity in 88% of cases and CD20 negativity in 90% of cases. Chemotherapy was administered to 80% of patients, with a complete response (CR) rate of 55%. The median overall survival (OS) was 32 months. In univariate analysis, HIV positive status showed better OS when compared with HIV negative status. In multivariate analysis, International Prognostic Index score, chemotherapy and CR were associated with survival benefit. Conclusion(s): This cohort, the largest reported to date, increases the spectrum of knowledge on PBL, rarely described. However, specific guidelines to clarify treatment are lacking, and may improve the poor prognosis of this rare disease.

[Determine the patient's position towards psychiatric care: a simple tool to estimate the alliance and the motivation]. / Déterminer la position du patient envers les soins psychiatriques avec le questionnaire Touriste-Plaignant-Client (TPC) : un outil simple pour évaluer l'alliance et la motivation.

OBJECTIVES: For the brief systemic therapy (BST), the evaluation of the patient's position towards the care is a prerequisite to psychotherapy. Three positions of the patient are described. The "tourist's" position: the patient claims to have no problem and doesn't suffer. Someone asks him to make an appointment, sometimes with threats. The "complaint's" position: the patient claims to suffer, but attributes the responsibility of this suffering to others. These two positions are not good for beginning a therapy. The "customer's" position differs from both previous positions. The "customer" considers that he has a psychological problem which depends on him and he is motivated in the resolution of it. In theory, the "customer" is more motivated and the therapeutic alliance is better. It is for this reason that the BST estimates the position of the patient at first, to bring the patient to the "customer's" position. The objective of this study is to assess an interview which identifies the patient's position towards the care, and to validate the theoretical elaborations of the brief systemic therapy. METHOD: The study concerns the follow-up of outpatients who consult a psychiatrist for the first time. The evaluation of the patients checks their position towards care using the Tourist-Complaint-Customer (TCC) inventory, how they suffer, the therapeutic alliance (scale Haq-2) and the compliance during care. The evaluation by the psychiatrists checks the suffering perceived, the motivation perceived and the diagnoses according to the DSM. RESULTS: The typology of these patients is made up of one half "complaint", a quarter of "tourist" and a quarter of "customer". The "customer's" position is correlated with the therapeutic alliance and the motivation perceived by the psychiatrist. The motivation perceived by the psychiatrist is correlated with the therapeutic alliance. These results correspond to the theoretical elaborations of the BST. CONCLUSION: the TCC inventory provides information on the motivation and the therapeutic alliance. If the patient is in "tourist" or "complaint" position, we recommend that the psychiatrist "work" to bring the patient to "customer" position. The evaluation of the position of the patient is simple and rich in information. We recommend that it be given a place in the daily practice of psychiatry.

Body fat distribution in HIV-infected patients treated for 96 weeks with darunavir/ritonavir monotherapy versus darunavir/ritonavir plus nucleoside reverse transcriptase inhibitors: the MONOI-ANRS136 substudy.

OBJECTIVES: The aim of the study was to evaluate fat tissue distribution in HIV-infected patients with suppressed viraemia treated with darunavir/ritonavir (darunavir/r) monotherapy versus darunavir/r triple therapy. METHODS: This study was a substudy of the randomized, multicentre, open-label MONOI-ANRS 136 trial. Body fat distribution and metabolic parameters were measured at baseline, week 48 and week 96. RESULTS: In total, 156 patients of the 225 initially enrolled in the MONOI trial participated in this study, 75 in the darunavir/r monotherapy arm and 81 in the darunavir/r triple-therapy arm. The median limb fat increase from baseline was +0.34 kg [interquartile range (IQR) -0.040 to +1.140 kg; P < 0.001] at week 48 and +0.33 kg (IQR -0.14 to +1.26 kg; P = 0.001) at week 96 in the monotherapy arm, while there was no change (-0.02 kg; IQR -0.53 to +0.52 kg) at week 48 and then an increase of +0.23 kg (IQR -0.45 to +0.87 kg; P = 0.046) at week 96 in the triple-therapy arm. The two arms differed significantly at week 48 (P = 0.001) but not at week 96. The median increase in trunk fat was +0.73 kg (IQR -0.24 to +1.60 kg; P < 0.001) and 0.60 kg (IQR -0.41 to +1.49 kg; P = 0.03) at week 48 and +1.16 kg (IQR -0.17 to +2.75 kg; P < 0.001) and +0.90 kg (IQR -0.51 to +2.34 kg; P = 0.001) at week 96 in the monotherapy and triple-therapy arms, respectively, with no difference between arms. At week 96, the only biological change was a glucose level elevation in the monotherapy arm (median +4.0 mg/dL; IQR -4.0 to +7.0 mg/dL) compared with the triple-therapy arm (P = 0.012). CONCLUSIONS: Overall, body fat tissue increased in patients on darunavir/r monotherapy and triple therapy, with no difference between the arms over 96 weeks. The only difference found was a delayed increase in limb fat tissue in the triple-therapy arm compared with the monotherapy arm in the first year.

Carbon-carbon-linked (pyrazolylphenyl)oxazolidinones with antibacterial activity against multiple drug resistant gram-positive and fastidious gram-negative bacteria.

In an effort to expand the spectrum of activity of the oxazolidinone class of antibacterial agents to include Gram-negative bacteria, a series of new carbon-carbon linked pyrazolylphenyl analogues has been prepared. The alpha-N-substituted methyl pyrazole (10alpha) in the C3-linked series exhibited very good Gram-positive activity with MICs

Substituent effects on the antibacterial activity of nitrogen-carbon-linked (azolylphenyl)oxazolidinones with expanded activity against the fastidious gram-negative organisms Haemophilus influenzae and Moraxella catarrhalis.

A series of new nitrogen-carbon-linked (azolylphenyl)oxazolidinone antibacterial agents has been prepared in an effort to expand the spectrum of activity of this class of antibiotics to include Gram-negative organisms. Pyrrole, pyrazole, imidazole, triazole, and tetrazole moieties have been used to replace the morpholine ring of linezolid (2). These changes resulted in the preparation of compounds with good activity against the fastidious Gram-negative organisms Haemophilus influenzae and Moraxella catarrhalis. The unsubstituted pyrrolyl analogue 3 and the 1H-1,2,3-triazolyl analogue 6 have MICs against H. influenzae = 4 microgram/mL and M. catarrhalis = 2 microgram/mL. Various substituents were also placed on the azole moieties in order to study their effects on antibacterial activity in vitro and in vivo. Interesting differences in activity were observed for many analogues that cannot be rationalized solely on the basis of sterics and position/number of nitrogen atoms in the azole ring. Differences in activity rely strongly on subtle changes in the electronic character of the overall azole systems. Aldehyde, aldoxime, and cyano azoles generally led to dramatic improvements in activity against both Gram-positive and Gram-negative bacteria relative to unsubstituted counterparts. However, amide, ester, amino, hydroxy, alkoxy, and alkyl substituents resulted in no improvement or a loss in antibacterial activity. The placement of a cyano moiety on the azole often generates analogues with interesting antibacterial activity in vitro and in vivo. In particular, the 3-cyanopyrrole, 4-cyanopyrazole, and 4-cyano-1H-1,2,3-triazole congeners 28, 50, and 90 had S. aureus MICs

Novel 1,5-diphenylpyrazole nonnucleoside HIV-1 reverse transcriptase inhibitors with enhanced activity versus the delavirdine-resistant P236L mutant: lead identification and SAR of 3- and 4-substituted derivatives.

Through computationally directed broad screening, a novel 1, 5-diphenylpyrazole (DPP) class of HIV-1 nonnucleoside reverse transcriptase inhibitors (NNRTIs) has been discovered. Compound 2 (PNU-32945) was found to have good activity versus wild-type (IC(50) = 2.3 microM) and delavirdine-resistant P236L (IC(50) = 1.1 microM) reverse transcriptase (RT). Also, PNU-32945 has an ED(50) for inhibition of viral replication in cell cultures of 0.1 microM and was shown to be noncytotoxic with a CC(50) > 10 microM. Structure-activity relationship studies on the 3- and 4-positions of PNU-32945 led to interesting selectivity and activity within the class. In particular, the 3-hydroxyethyl-4-ethyl congener 29 is a potent inhibitor of the P236L mutant (IC(50) = 0.65 microM), whereas it is essentially inactive versus the wild-type enzyme (IC(50) > 50 microM). Furthermore, this compound was significantly more active versus the P236L mutant than delavirdine. The synthesis and RT inhibitory activity of various 3- and 4-substituted analogues are discussed.

Synthesis and structure-activity relationships of the (alkylamino)piperidine-containing BHAP class of non-nucleoside reverse transcriptase inhibitors: effect of 3-alkylpyridine ring substitution.

Development of resistance to currently approved HIV therapies has continued to fuel research efforts to improve the metabolic stability and spectrum of activity of the (alkylamino)piperidine-containing bis(heteroaryl)piperazine (AAP-BHAP) class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). The synthesis of analogues in which the usual 3-alkylamino substituent on the pyridine ring is replaced by a 3-alkyl substituent led to compounds which retained activity against recombinant P236L and wild-type (WT) reverse transcriptase (RT), while inhibition of the Y181C mutant RT was reduced relative to the activity of the 3-alkylamino-substituted congeners. Testing of representative analogues in an in vitro liver microsome assay indicated that the alkyl substituent would not appreciably improve the metabolic stability of the AAP-BHAP template. In vivo pharmacokinetic evaluation of three compounds confirmed these results in that high systemic clearances were observed. Nevertheless, one compound (13), PNU-103657, possessed oral bioavailability in rats approaching that of the structurally related NNRTI drug delavirdine which is currently on the market for the treatment of HIV infection.

Synthesis and bioactivity of novel bis(heteroaryl)piperazine (BHAP) reverse transcriptase inhibitors: structure-activity relationships and increased metabolic stability of novel substituted pyridine analogs.

The major route of metabolism of the bis(heteroaryl)piperazine (BHAP) class of reverse transcriptase inhibitors (RTIs), atevirdine and delavirdine, is via oxidative N-dealkylation of the 3-ethyl- or 3-isopropylamino substituent on the pyridine ring. This metabolic pathway is also the predominant mode of metabolism of (alkylamino)piperidine BHAP analogs (AAP-BHAPs), compounds wherein a 4-(alkylamino)piperidine replaces the piperazine ring of the BHAPs. The novel AAP-BHAPs possess the ability to inhibit non-nucleoside reverse transcriptase inhibitor (NNRTI) resistant recombinant HIV-1 RT and NNRTI resistant variants of HIV-1. This report describes an approach to preventing this degradation which involves the replacement of the 3-ethyl- or 3-isopropylamino substituent with either a 3-tert-butylamino substituent or a 3-alkoxy substituent. The synthesis, bioactivity and metabolic stability of these analogs is described. The majority of analogs retain inhibitory activities in enzyme and cell culture assays. In general, a 3-ethoxy or 3-isopropoxy substituent on the pyridine ring, as in compounds 10, 20, or 21, resulted in enhanced stabilities. The 3-tert-butylamino substituent was somewhat beneficial in the AAP-BHAP series of analogs, but did not exert a significant effect in the BHAP series. Lastly, the nature of the indole substitution sometimes plays a significant role in metabolic stability, particularly in the BHAP series of analogs.

Dopamine receptor modulation by a highly rigid spiro bicyclic peptidomimetic of Pro-Leu-Gly-NH2.

A peptidomimetic analogue of Pro-Leu-Gly-NH2 (PLG), compound 3, has been synthesized that contains a highly constrained spiro bicyclic type-II beta-turn mimic. Peptidomimetic 3 enhanced the binding of the dopamine receptor agonist ADTN to dopamine receptors by 40% at 10(-6) M. At this same concentration PLG enhanced the binding of ADTN by 26%. Like PLG, 3 exhibited a bell-shaped dose-response curve with the maximum effect occurring at a concentration of 10(-6) M. Because of the highly rigid nature of the spiro bicyclic type-II beta-turn constraint found in 3, these results lend strong support for the hypothesis that the biologically active conformation of PLG is a type-II beta-turn.

Diuretic-induced azotemia: unmasking the role of increased peripheral catabolism through evisceration-hepatectomy.

By abolishing the large splanchnic uptake of amino acids, evisceration-hepatectomy unmasks the tendency for peripheral tissues to release increased amounts of amino acids into the extracellular fluid during sodium depletion. The increase in amino acid delivery to the liver may stimulate hepatic urea synthesis both by providing more substrates for conversion to urea and perhaps also by stimulation of the activity of urea cycle enzymes.

Relationship between metabolism and radioprotective activity of 2-phenylthiazolidine and its m-bromo derivative.

Molecular biotransformation of 2-phenylthiazolidine (1) and its m-bromo derivative (2) in the mouse is followed by autoradiographic studies and assessed by analysis of urinary metabolites. Cysteamine (4) is one of the metabolites of compounds 1 and 2. Radioprotective activity and efficacy over a period of time of 1, 2, and 4 correlate closely with distribution and metabolism.