Perception de la tension au travail (job strain) en milieu hospitalier à Pointe-Noire, Congo-Brazzaville / Perception of job strain in the hospital environment at Pointe-Noire, Congo-Brazzaville

Objectif : Evaluer la situation de job strain et les manifestations psychosomatiques ressenties par les personnels soignants des hôpitaux de Pointe-Noire. Méthodologie : L'étude était une enquête transversale analytique. Un auto-questionnaire monté selon le modèle « demande-contrôle-soutien ¼ de KARASEK, avait été utilisé pour recueillir de manière anonyme des données sociodémographiques, des informations relatives à l'état de santé, à leur poste de travail et d'identifier des facteurs de risques psychosociaux. Résultats : Sur l'ensemble des cent cinquante (150) soignants retenus, 47,02% présentaient une faible latitude décisionnelle contre 52,98% avec une forte latitude. La forte demande psychologique était perçue par 50,33% des soignants contre 49,67% avec une faible demande. La situation de job strain était retrouvée chez 26,67% des soignants. Les services des urgences et de médecine étaient les plus exposés avec respectivement 25% et 20% du personnel en situation de job strain. Une faible ancienneté au travail prédisposait à une perception de job strain plus élevée. Les médecins spécialistes et les infirmiers représentaient les catégories professionnelles les plus tendus avec respectivement 42,86% et 30,23% des individus concernés. Un lien statistique était retrouvé entre d'une part le job strain et d'autre part les troubles musculosquelettiques et l'auto-estimation de l'impact du travail sur la santé. Conclusion : Les risques psychosociaux notamment le stress sont une préoccupation réelle dans les établissements de soins et cette enquête a permis de noter qu'ils pourraient avoir des conséquences sur la santé des soignants à Pointe-Noire.

Objective: To assess the job strain situation and the psychosomatic manifestations felt by the health care worker of the Pointe-Noire hospitals. Methodology: It was an analytical cross-sectional survey. A self-questionnaire set up according to the KARASEK "demand-control-support" model had been used to anonymously collect sociodemographic data, information on their health situation, at their workplace and identify psychosocial risk factors. Results: of one hundred and fifty (150) caregivers considered, 47.02% had low decision latitude versus 52.98% with high latitude. The high psychological demand was felt by 50.33% of the medics versus 49.67% with a low demand. The job strain situation was found among 26.67% of medics. Emergency and medical departments were the most exposed with 25% and 20% of staff in a job-strain situation respectively. Low job seniority predisposed to a higher feeling of job-strain. Specialist doctors and nurses represented the most strained professional categories with 42.86% and 30.23% of the individuals concerned respectively. A statistical relation was found between job strain on the one hand and musculoskeletal trouble and self-estimation of the impact of work on health on the other hand. Conclusion: Psychosocial risks, particularly stress, are a real concern in health institutions and this survey note that there could be impact on medics' health in Pointe-Noire.

Efficacy of an agonist of α-MSH, the palmitoyl tetrapeptide-20, in hair pigmentation.

OBJECTIVE: Hair greying (i.e., canities) is a component of chronological ageing and occurs regardless of gender or ethnicity. Canities is directly linked to the loss of melanin and increase in oxidative stress in the hair follicle and shaft. To promote hair pigmentation and reduce the hair greying process, an agonist of α-melanocyte-stimulating hormone (α-MSH), a biomimetic peptide (palmitoyl tetrapeptide-20; PTP20) was developed. The aim of this study was to describe the effects of the designed peptide on hair greying. METHODS: Effect of the PTP20 on the enzymatic activity of catalase and the production of H2 O2 by Human Follicle Dermal Papilla Cells (HFDPC) was evaluated. Influence of PTP20 on the expression of melanocortin receptor-1 (MC1-R) and the production of melanin were investigated. Enzymatic activity of sirtuin 1 (SIRT1) after treatment with PTP20 was also determined. Ex vivo studies using human micro-dissected hairs allowed to visualize the effect of PTP20 on the expression in hair follicle of catalase, TRP-1, TRP-2, Melan-A, ASIP, and MC1-R. These investigations were completed by a clinical study on 15 human male volunteers suffering from premature canities. RESULTS: The in vitro and ex vivo studies revealed the capacity of the examined PTP20 peptide to enhance the expression of catalase and to decrease (30%) the intracellular level of H2 O2 . Moreover, PTP20 was shown to activate in vitro and ex vivo the melanogenesis process. In fact, an increase in the production of melanin was shown to be correlated with elevated expression of MC1-R, TRP-1, and Melan-A, and with the reduction in ASIP expression. A modulation on TRP-2 was also observed. The pivotal role of MC1-R was confirmed on protein expression analysed on volunteer's plucked hairs after 3 months of the daily application of lotion containing 10 ppm of PTP20 peptide. CONCLUSION: The current findings demonstrate the ability of the biomimetic PTP20 peptide to preserve the function of follicular melanocytes. The present results suggest potential cosmetic application of this newly designed agonist of α-MSH to promote hair pigmentation and thus, reduce the hair greying process.

Study of gene expression alteration in male androgenetic alopecia: evidence of predominant molecular signalling pathways.

BACKGROUND: Male androgenetic alopecia (AGA) is the most common form of hair loss in men. It is characterized by a distinct pattern of progressive hair loss starting from the frontal area and the vertex of the scalp. Although several genetic risk loci have been identified, relevant genes for AGA remain to be defined. OBJECTIVES: To identify biomarkers associated with AGA. METHODS: Molecular biomarkers associated with premature AGA were identified through gene expression analysis using cDNA generated from scalp vertex biopsies of hairless or bald men with premature AGA, and healthy volunteers. RESULTS: This monocentric study reveals that genes encoding mast cell granule enzymes, inflammatory mediators and immunoglobulin-associated immune mediators were significantly overexpressed in AGA. In contrast, underexpressed genes appear to be associated with the Wnt/ß-catenin and bone morphogenic protein/transforming growth factor-ß signalling pathways. Although involvement of these pathways in hair follicle regeneration is well described, functional interpretation of the transcriptomic data highlights different events that account for their inhibition. In particular, one of these events depends on the dysregulated expression of proopiomelanocortin, as confirmed by polymerase chain reaction and immunohistochemistry. In addition, lower expression of CYP27B1 in patients with AGA supports the notion that changes in vitamin D metabolism contributes to hair loss. CONCLUSIONS: This study provides compelling evidence for distinct molecular events contributing to alopecia that may pave the way for new therapeutic approaches.

Both plants Sebastiania chamaelea from Niger and Chrozophora senegalensis from Senegal used in African traditional medicine in malaria treatment share a same active principle.

ETHNOPHARMACOLOGICAL RELEVANCE: Based on ethnobotanical data obtained from Nigerien and Senegalese traditional healers, two Euphorbiaceae plants, Sebastiania chamaelea and Chrozophora senegalensis, traditionally used to treat malaria, were selected for further investigations. MATERIALS AND METHODS: Plant extracts were prepared with different solvents and tested both in vitro on several strains of Plasmodium falciparum, and in vivo to evaluate their antiplasmodial properties and isolate their active principles. RESULTS: With IC50 values around 6.5µg/ml and no significant cytotoxicity (>50µg/ml), the whole plant aqueous extract from S. chamaelea showed the best in vitro results. In vitro potentiation assays showed strong synergistic activity of S. chamaelea extract with the antiplasmodial drug chloroquine on the chloroquine-resistant P. falciparum strain W2-Indochina. In other respects, the aqueous crude extract of C. senegalensis leaves showed the most significant antiplasmodial activity in vitro (IC50 values less than 2µg/ml). We also demonstrated the prophylactic activity of C. senegalensis in vivo in a murine malaria model. Bioassay-guided fractionation of aqueous extracts of these plants enabled the isolation and identification of ellagic acid (EA, 1) as the main compound responsible for their antiplasmodial activity. Together with EA, other derivatives belonging to different chemical groups were isolated but showed moderate antimalarial activity: gallic acid (2), brevifolin carboxylic acid (3), protocatechuic acid (4), corillagin (5), rutin (6) and 3,4,8,9,10-pentahydroxy-dibenzo(b,d)pyran-6-one (7). The structures were determined by the usual spectroscopic methods and by comparison with published data. Furthermore, we report here the quantification of compound 1 (EA) by RP-HPLC in the dried extracts of these plants, reported for the first time in both these species, and possessing the highest in vitro antiplasmodial activity with IC50 values from 180 to 330nm. CONCLUSIONS: These in vitro and in vivo results support the traditional use in Africa of crude extracts of both S. chamaelea and C. senegalensis as an antimalarial treatment and prove the significant antiplasmodial property of EA.

The regulatory role of the tetrapeptide AcSDKP in skin and hair physiology and the prevention of ageing effects in these tissues--a potential cosmetic role.

The naturally occurring tetrapeptide acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) recognized as a potent angiogenic factor was shown recently to contribute to the repair of cutaneous injuries. In the current article, we report the ability of AcSDKP to exert a beneficial effect on normal healthy skin and scalp and to compensate for the ageing process. In vitro AcSDKP at 10⁻¹¹-10⁻7 M significantly stimulates the growth of human keratinocytes, fibroblasts and follicle dermal papilla cells. Moreover, it enhances the growth of human epidermal keratinocyte progenitor and stem cells as shown in a clonogenic survival assay. Topical treatment of ex vivo cultured skin explants with 10⁻5 M AcSDKP increases the thickness of the epidermis and upregulates the synthesis of keratins 14 and 19, fibronectin, collagen III and IV as well as the glycoaminoglycans (GAGs). In the ex vivo-cultured hair follicles, AcSDKP promotes hair shaft elongation and induces morphological and molecular modifications matching the criteria of hair growth. Furthermore, AcSDKP at 10⁻¹¹-10⁻7 M was shown to improve epidermal barrier, stimulating expression of three protein components of tight junctions (claudin-1, occludin, ZO-1) playing an important role in connecting neighbouring cells. This tetrapeptide exercises also activation of SIRT1 implicated in the control of cell longevity. Indeed, a two-fold increase in the synthesis of SIRT1 by cultured keratinocytes was observed in the presence of 10⁻¹¹-10⁻7 M AcSDKP. In conclusion, these findings provide convincing evidence of the regulatory role of AcSDKP in skin and hair physiology and suggest a cosmetic use of this natural tetrapeptide to prevent skin ageing and hair loss and to promote the cutaneous regeneration and hair growth.

Sentinel node biopsy and neoadjuvant chemotherapy in the treatment of breast cancer.

PURPOSE: Sentinel lymph node biopsy (SLNB) has become a safe and accurate alternative to axillary lymph node dissection (ALND) in the surgical management of early breast cancer. The aim of this study was to determine the false negative rate of SLNB in patients with advanced breast cancer after neoadjuvant chemotherapy. METHODS: Forty-eight patients with 49 advanced breast cancers (one patient had bilateral disease) underwent neoadjuvant chemotherapy. All of them had SLNB, followed by standard level I/II ALND. SLNs were identified in 47 out of 49 tumors (detection rate 95.9%). RESULTS: Axillary nodal metastases were detected in 28 patients; SLNs were positive only in 14 patients. Four sentinel internal mammary nodes were removed in 4 patients, while one of them was positive with micrometastasis but axillary nodes were negative. False-negative results occurred in 2 (7.14%) patients. The results of our study confirm that SLNB in patients with advanced breast cancer is not significantly altered by the preoperative chemotherapy. Biopsy results were very similar to those without any neoadjuvant chemotherapy. CONCLUSION: ALND, known for its serious complications, can be replaced in some cases by SLNB.

[Lymphatic mapping and biopsy of sentinel lymph nodes using combined methodology of in vivo application of Patentblue and radionuclide and ex vivo detection of metastatic affection of lymph nodes in colorectal carcinoma]. / Lymfatické mapování a biopsie sentinelových uzlin s pouzitím kombinované metodiky in vivo aplikace Patentblue a radiokoloidu a ex vivo detekce metastatického postizení lymfatických uzlin u kolorektálního karcinomu.

AIM OF THE STUDY: to check the new technique of lymphatic mapping and sentinel node biopsy by colorectal cancer surgery and to improve the lymphatic staging. METHOD: combined technique of lymphatic mapping via Patentblue and the radiocolloid in vivo applied in the rectal cancer surgery. The lymphatic-mapping technique with Patentblue in the colon cancer surgery. Radically or palliative tumour resection. Ex vivo detection of sentinel and non-sentinel lymph nodes in the specimen and their division into peritumoral, intermedial and central level. Serial sectioning examination and immunohistochemistry examination of detected lymph nodes. Statistic process. RESULTS: The methods were used for 107 patients. 1985 lymph nodes were examined, out of which 208 was with metastasis. Positive nodes were detected in 56 patients. In average there were 18.5 nodes per patient. 966 sentinel nodes were detected by colouring and radiocolloid marking. Sentinel nodes showed in 97 patients. In 10 patients, the method failed. In 44 patients, sentinel nodes were positive; 117 positive nodes in total. Skip metastases were detected in 6 percent of the patients. The upstaging of metastatic detection was in 3.7 percent. CONCLUSION: The technique of lymphatic mapping and sentinel node detection significantly increases the number of detected nodes and selects the marks the sentinel ones for further examination. The greatest amount of findings of nodal metastases is in the area closest to the tumour, therefore, when sentinel nodes are negative there, these can be examined more closely, by the method of serial insections or immunohistochemically, and staging of the disease can be made more accurate.

[Sentinel lymph node biopsy in the breast carcinoma in clinical practice]. / Biopsie sentinelové uzliny u karcinomu prsu v klinické praxi.

AIM: In the management of early breast carcinoma, biopsy of sentinel lymph nodes has gradually replaced dissection of Level I and II axillary nodes. The aim of the study is to assess feasability and reliability of the method in our conditions. METHOD: From June 1998 to June 2007, a total of 458 sentinel node biopsies (SLNB) were performed. Originally, patent blue sentinel node mapping was used. Since 2000, a combination of radiocolloid application and a gamma- probe (detector), as well as the patent blue, has been used. Originally, SLNBs were followed by axillary dissections, however, in 2002, the procedure was waived in cases of negative sentinel nodes findings. RESULTS: Out of the total of 458 SLNB patients, 382 female patients were included in the study. SLNB, without concomitant axillary dissection, was performed in 170 subjects. In 70 subjects, the sentinel node was positive and they were indicated for axillary dissections. Positive non-sentinel nodes were detected 17 times. In total, 899 sentinel nodes were examined in the study group of 382 biopsies. The mean was 2.35. False negative nodes were recorded in three cases in female patients with SLNB and axillary dissection (4.6%). No local relapses in the axilla were recorded in negative sentinel node findings without subsequent axillary dissections. CONCLUSION: Sentinel node biopsy is a safe alternative to axillary dissection in the surgical management of early breast carcinoma.

[Distribution of metastatic affection in colorectal carcinoma using lymphatic mapping and radiation-navigated biopsy of the sentinel lymph node]. / Distribuce metastatického postiienif u kolorektálního karcinomu s pouzitím metody lymfatického mapování a radiacne navigované biopsie sentinelové uzliny.

AIM: The aim is to define distribution of the lymphonode metastatic affection in colorectal carcinoma and to evaluate a new methodology of lymphatic mapping and the sentinel lymphonode detection during colorectal carcinoma procedures in practice. USED METHODS: A method of peroperative lymphatic mapping using a Patentblue method in vivo. Rectoscopic peritumoral application of a radiocoloid in a two-day or a single-day protocol, scintigraphy, peroperative quants of radioactivity detection using a gamma probe. Radical or paliative tumor resection. Detection of the sentinel and non-sentinel nodes on a preparation ex vivo, divided according to levels. The metastatic affection distribution is assessed in three levels, marked U1 - U3, a S1 - S3. Histopathological examination of the nodes on series sections and, event, immunohistochemistry. RESULTS: The methods were used in 66 patients. A total of 970 nodes have been examined, with an average of 14.6 nodes/ patient. The metastases quantity decreases with distance from the tumor. The peritumoral levels (U1a S1) record the highest rates of metastases. In our patient group, 92% of the metastases were recorded in the S1 level, 4% in the S2 level and 4 % in the S3 level. CONCLUSIONS: The highest rate of metastases was recorded in the levels, closest to the tumor, therefore, in case of negative findings of sentinel nodes in the S1 level, the nodes from this level may be closely examined (using the method of series sections and immunhistochemistry) and the staging be established more precisely.

[New aspects of diabetes]. / Nouveaux aspects du diabète.

Type II diabetes is a serious, insidious disease which is growing at an impressive rate, with 200 million diabetics worldwide and as many who ignore their state. Having been seriously studied over more than a century and a half, an enormous quantity of knowledge regarding this disease has been accumulated. The research we are conducting has allowed us to identify the most important actors responsible for diabetes. These are glucose which leads to glyoxal and to methylglyoxal which in turn reacts with innumerable targets in the organism (including insulin) unless prevented from doing so by detoxifying mechanisms (e.g., glyoxalases). The role of microorganisms in the occurrence and development of diabetes has also to be seriously examined.

[Lymphadenectomy in the early gastric carcinoma]. / Lymfadenektomie u casného karcinomu zaludku.

AIM: The method of extended lymphadenectomy in the early gastric carcinoma treatment remains controversial. The aim of this prospective study is to assess the above method feasibility with acceptable rates of complications, in our conditions. METHODOLOGY: From 2000 to 2003, 11 patients with early carcinomas of the stomach were treated using the method of extended lymphadenectomy. The study group included 7 males and 4 females. RESULTS: In 6 cases, the tumors were located in the distal, in 4 cases in the middle and once in the proximal third of the stomach. In a single case, the IIIA stadium was concerned, the other cases were rated lower. In total, 205 lymphonodes measuring 18.6 on average (median of 16) were examined. The total of 5 lymphonodes were malignant, all of them were found in one patient. The method of the sentinel lymphonode biopsy was applied once. A cardiopulmonary complication was reported once, a punction of the subphrenic absces was reported once, a primary disorder causing a death was reported once and the patient concerned exited after a 14-month-period of his follow-up. Once, a local relaps of the disorder was reported 43 months after the procedure. The follow-up median was 27 months. CONCLUSION: The method of extended lymphadenectomy can be conducted even in our conditions with acceptable rates of complications.

[Surgical therapy of the ductal carcinoma in situ]. / Chirurgická terapie duktáilního karcinomu in situ.

AIM: Rates of the newly-detected DCIS reach up to 20% in developed countries. There is no unified therapeutic scheme to deal with the disorder. The aim of this work is to assess the author's own therapeutic results. METHODOLOGY: From 1999 until 2003, 11 female patients suffering from the DCIS were treated and 2 DCIS female patients were treated using microinvasion. The diagnosis was established 5x by the core-cut and 8x by the surgical excision. RESULTS: The size of the tumors varied from 0.5 cm to 6.0 cm. Conservative procedures were performed 11 times, a simple mastectomy once and a mastectomy with reconstruction once, as well. The sentinel lymphonodes were examined in all cases and once the examination was accompanied by the axilla dissection. The number of the sentinel lymphonodes was 29. All of the lymphonodes were negative. Seven female patients were given a complementary therapy. All female patients have had no local relapse in the breast and have had no signs of the disease process since. The average follow-up time is 13.5 months. CONCLUSION: The conservative procedures sufficiently provide treatment of early forms of the DCIS of the breast. The sentinel lymphonode biopsy is a patient- kind method, giving exact information on the status of the axillary lymphonodes and it is considered a suitable part of the DCIS therapy.

[Mini-invasive radiation-navigated parathyreoidectomy--MIRP]. / Miniinvazivní radiacne navigovaná paratyreoidektomie--MIRP.

AIM: The aim was to introduce a new surgical method and to verify its validity. METHODOLOGY: In 20 patients whose ultrasound findings correlated with the MIBI scintigraphic results, a radiation-navigated parathyreoidectomy using a C-Track was conducted, following a radionucleotide application. RESULTS: From 2001 to 2003, 20 patients with hyperparathyreosis were operated. In all cases, an altered parathyroid gland with increased activity was detected using radionavigation. After the surgery, the calcium and the parathormone blood levels decreased. CONCLUSION: The MIRP is a miniinvasive surgical method indicated for the use in cases when hyperparathyreosis is confirmed and the ultrasound findings correlate with the MIBI-scintigraphic findings.

[Sentinel lymph node biosy in surgical treatment of breast carcinoma: prospective study]. / Biopsie sentinelové uzliny v chirurgické lécbe karcinomu prsu: prospektivní studie.

OBJECTIVE: Authors report the validity and accuracy of lymphatic mapping with sentinel node biopsy in patients with early breast cancer between 1998 and 2000. TYPE OF STUDY: Prospective study. LOCATION: Department of Surgery, Atlas Hospital Zlin. METHODS USED: Lymphatic mapping and sentinel node biopsy using patentblue in patients with breast cancer was performed between 1998 and 2000. Combination of patentblue and radiocoloid Nanocoll Nycomed Amersham has been used from 2000. C-Track device (Care Wise Medical Product Morgan Hill) was applied for detection of radiocoloid in sentinel node. Gamma probe intraoperatively localised sentinel nodes. Lymphoscintigraphy was performed routinely. Patients were tested with routine hematoxylin & eosin staining. When the H&E staining in sentinel nodes was negative the immunohistochemical procedure was used. Following identification of sentinel nodes, axillary node dissection was applied. Axillary node dissection was abandoned by patients with tumor T1 and sentinel node negative. RESULTS: In 124 cases, the sentinel node was successfully identified. 122 patients were women with unilateral and one woman with bilateral cancer. 1 was a male. Of these 124 cases 60 were node-positive and sentinel nodes metastasis was in 26 cases only. 1375 nonsentinel nodes were examined (a mean 13.4). 268 sentinel nodes were examined (a mean 2.2). Hematoxylin and eosin staining was used routinely and if no tumor was identified then imunohistochemical cytokeratin staining was performed. Imunohistochemical staining was used in 21 cases. Only in one patient micrometastases were identified. Three sentinel nodes were negative in patient with axillary disease. CONCLUSION: This study demonstrates that sentinel node biopsy in patients with early breast cancer is safe and highly accurate an can be used to avoid axillary lymph node dissection.

Development of an enzyme immunoassay for a stable amidated analog of the hemoregulatory peptide acetyl-Ser-Asp-Lys-Pro.

The tetrapeptide Acetyl-Ser-Asp-Lys-Pro (AcSDKP) has been shown to protect hematopoietic stem cells from the toxicity of anticancer chemotherapies. Since its pharmacological efficacy is limited by a rapid degradation by Angiotensin-I Converting Enzyme (ACE), AcSDKP analogs resistant to ACE have been synthesized. One of these compounds (AcSDKP-NH,) differs from the native AcSDKP by amidation of the C-terminus. Further evaluations of this molecule require an analytical method in order to characterize its pharmacokinetic profile. We report, here, the development of a highly specific and sensitive enzyme immunoassay (EIA) for AcSDKP-NH, thatdoes not cross-react with endogenous or exogenous AcSDKP. Using AcSDKP-NH2-acetylcholinesterase conjugate as a tracer, rabbit specific antiserum and microtiter plates coated with goat anti-rabbit immunoglobulins, this EIA allows the determination of AcSDKP-NH2 with limits of quantitation of 1 nM in mouse plasma and 100 pmol/g in tissues. Intra-day and inter-day coefficients of variations were less than 20%. The method was successfully applied to a pharmacokinetic study in order to compare plasma and tissue profiles of AcSDKP-NH2 and AcSDKP. Plasma AcSDKP-NH2 levels were found higher than those of AcSDKP, with AUCinf and Cmax values, respectively, 26- and 10-fold higher than that of AcSDKP.

Synthesis and biological evaluation of analogues of the tetrapeptide N-Acetyl-Ser-Asp-Lys-Pro (AcSDKP), an inhibitor of primitive haematopoietic cell proliferation.

The tetrapeptide N-Acetyl-Ser-Asp-Lys-Pro (AcSDKP), an inhibitor of haematopoietic stem cell proliferation, reduces in vivo and in vitro the damage to the stem cell compartment resulting from treatment with chemotherapeutic agents or ionizing radiations. In order to provide new molecules likely to improve the myeloprotection displayed by this tetrapeptide, we have prepared a set of analogues of AcSDKP. These compounds are derived from the parent peptide by substitution or modification of the N- or of the C-terminus, or substitution of side chains. We report here that almost all investigated analogues retain the antiproliferative activity reducing in vitro the proportion of murine Colony-Forming Units Granulocyte, Macrophage (CFU-GM) in S-phase and inhibiting the entry into cycle of High Proliferative Potential Colony-Forming Cells (HPP-CFC). This shows that the polar groups of Ser, Asp or Lys are critical for the expression of biological activity, but that the modification of the N- or C-terminus mostly yielded compounds still retaining antiproliferative activity and devoid of toxicity. The efficacy of AcSDKP analogues in preventing in vitro the primitive haematopoietic cells from entering into cycle makes these molecules new candidates for further in vivo investigations.

Pulsed Doppler tissue imaging of the velocity of tricuspid annular systolic motion; a new, rapid, and non-invasive method of evaluating right ventricular systolic function.

AIMS: Rapid, accurate, and widely available non-invasive evaluation of right ventricular function still presents a problem. The purpose of the study was to determine whether the parameters derived from Doppler tissue imaging of tricuspid annular motion could be used as indexes of right ventricular function in patients with heart failure. METHODS: Standard and pulsed Doppler tissue echocardiography were obtained in 44 patients with heart failure (mean left ventricular ejection fraction 24 +/- 7%) and in 30 age- and sex-matched healthy volunteers. The tricuspid annular systolic and diastolic velocities were acquired in apical four-chamber views at the junction of the right ventricular free wall and the anterior leaflet of the tricuspid valve using Doppler tissue imaging. Within 2 h of Doppler tissue imaging, the first-pass radionuclide ventriculogram, determining right ventricular ejection fraction and equilibrium gated radionuclide ventriculography single photon emission computed tomography, were performed in all patients. RESULTS: In patients with heart failure, the peak systolic annular velocity was significantly lower and the time from the onset of the electrocardiographic QRS complex to the peak of systolic annular velocity was significantly greater than the corresponding values in healthy subjects (10.3 +/- 2.6 cm. s(-1) vs 15.5 +/- 2.6 cm.s(-1), P < 0.001, and 198 +/- 34ms vs 171 +/- 29 ms, P < 0.01, respectively). There was a good correlation between systolic annular velocity and right ventricular ejection fraction (r = 0.648, P <0.001). A systolic annular velocity < 11.5 cm.s(-1)predicted right ventricular dysfunction (ejection fraction < 45%) with a sensitivity of 90% and a specificity of 85%. CONCLUSION: We conclude that the evaluation of peak systolic tricuspid annular velocity using Doppler tissue imaging provides a simple, rapid, and non-invasive tool for assessing right ventricular systolic function in patients with heart failure.

Captopril inhibits in vitro and in vivo the proliferation of primitive haematopoietic cells induced into cell cycle by cytotoxic drug administration or irradiation but has no effect on myeloid leukaemia cell proliferation.

Angiotensin I-converting enzyme (ACE) has been shown to be involved in the catabolism of the tetrapeptide acetyl-Ser-Asp-Lys-Pro (AcSDKP). As AcSDKP is a physiological inhibitor of haematopoietic stem cell proliferation, we investigated the in vitro and in vivo effects of captopril, one of the specific inhibitors of ACE, on the proliferation of primitive haematopoietic cells. Regenerating bone marrow cells obtained from mice given one injection of cytosine arabinoside (100 mg/kg) as well as SA2 myeloid leukaemia cells were incubated in vitro for 24 h with 10-6 M captopril. Captopril significantly reduced the proportion of high proliferative potential colony-forming cells (HPP-CFC-1) in S-phase, whereas it had no effect on the proportion of SA2 leukaemic colony-forming cells in S-phase. When given in vivo to mice 1 h after 2 Gy gamma-irradiation or cytosine arabinoside (AraC) injection, captopril (100 mg/kg) was shown to prevent HPP-CFC-1 entry into S-phase induced by these cytotoxic treatments. The observed effects correlated with a reduction in ACE degradative activity and an increase in the level of endogenous AcSDKP both in the supernatants of captopril-treated bone marrow cells and in plasma of treated animals. The present findings suggest that AcSDKP might mediate the observed in vitro and in vivo inhibitory effects of captopril on primitive haematopoietic cell proliferation.

Source, catabolism and role of the tetrapeptide N-acetyl-ser-asp-lys-Pro within the testis.

The tetrapeptide N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (AcSDKP) is a natural regulator of hematopoietic stem cell proliferation. The present study was aimed at investigating the presence and the role of AcSDKP in rat testis. Specific immunoreactivity was always observed in the interstitial tissue at all stages of testicular development and in elongated spermatids at 45 days of age and in adults. In accordance with the interstitial labeling, high AcSDKP levels were detected in Leydig cell and testicular macrophage culture media and cell extracts, as well as in the testicular interstitial fluid (TIF). Much lower concentrations were found in peritubular cells and Sertoli cells cultures, whereas very low concentrations were present in cultured spermatocytes and spermatids. In contrast to the slight degradation rate of AcSDKP observed in the spermatocyte and spermatid culture media, no catabolism of the peptide was seen in testicular somatic cell culture medium. Furthermore, the degradation rate of AcSDKP was much lower in TIF than in peripheral blood plasma. Despite the very strong evidence indicating that Leydig cells and testicular macrophages produce AcSDKP, the selective destruction of these cells did not result in any change in AcSDKP levels in TIF or in plasma. This suggests a compensatory mechanism ensuring constant levels of the peptide in TIF when interstitial cells are absent. Finally, in vitro, in the presence of AcSDKP, significantly more [(3)H]thymidine incorporation was found in A spermatogonia. In conclusion, this study establishes the presence of very high concentrations of AcSDKP in rat testis and demonstrates its Leydig cell and testicular macrophage origin. The presence of AcSDKP in the TIF and its stimulatory effect on thymidine incorporation in spermatogonia very strongly suggest its implication in the paracrine control of spermatogenesis.

Captopril inhibits the proliferation of hematopoietic stem and progenitor cells in murine long-term bone marrow cultures.

Drugs used mainly for the treatment of hypertension, such as angiotensin I-converting enzyme (ACE) inhibitors, can cause pancytopenia. The underlying cause of this side effect remains unknown. In the present study, long-term bone marrow cultures (LTBMCs) were utilized to evaluate the role of captopril (D-3-mercapto-2-methylpropionyl-L-proline), one of the potent ACE inhibitors, in regulating hematopoietic stem/progenitor cell proliferation. Captopril (10(-6) M final concentration) was added to LTBMCs at the beginning of the culture period and at weekly intervals for six weeks. There was no toxicity to the bone marrow cells as measured by the unchanged cell number in the nonadherent layer during the whole culture period, and there was an increased cellularity of the adherent layer at the end of the six weeks of treatment. However, captopril decreased the proportion of granulocyte-macrophage colony-forming cells (GM-CFCs) in S phase at weeks 2 and 3 as well as that of high proliferative potential colony-forming cells (HPP-CFCs) at week 3 in the nonadherent layer. There was no change in the kinetics of the GM-CFCs and HPP-CFCs present in the adherent layer. These results suggest that captopril causes myelosuppression by inhibiting hematopoietic cell proliferation of progenitor and stem cells rather than depleting cells of the bone marrow microenvironment.