Another case of dyshidrosiform pemphigoid.
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Aged↗
Biomedical subjects
L Benassi
Publications and source records attributed to L Benassi.
Ultraviolet B radiation induces activation of neutral and acidic sphingomyelinases and ceramide generation in cultured normal human keratinocytes.
The sphingomyelin pathway is an ubiquitous, evolutionary conserved signaling system which transduces an extracellular signal into the cell. During the past few years increasing evidence has shown that the sphingolipid ceramide may play a role as a second messenger in intracellular signal transduction. The ceramide generation via sphingomyelinase (SMase) is followed by three major cellular responses: cell growth arrest, induction of cell differentiation and/or induction of programmed cell death or apoptosis. The aim of this study is to investigate whether activation of SMases and generation of ceramide can be induced by UVB radiation in normal human keratinocytes. The present data show that exposure to UVB radiation results in rapid generation of ceramide. The ceramide accumulation starts 15 min after UV exposure and progressively increases up to 24 h. In vitro measurement of SMase activity following exposure to UVB evidences an activation of both neutral and acidic SMases. Moreover, UVB induces apoptosis in normal human keratinocytes as shown by TUNEL technique and FACS analysis. These data indicate that UVB induced ceramide generation and activation of both neutral and acidic SMases, suggesting that sphingolipids metabolism may be involved in the UVB signaling pathway.
Apoptosis↗
Abdominal or vaginal hysterectomy for enlarged uteri: a randomized clinical trial.
OBJECTIVE: The purpose of this study was to compare advantages, disadvantages, and outcomes in patients who undergo vaginal or abdominal hysterectomy for enlarged symptomatic uteri. STUDY DESIGN: In a prospective, randomized study, 60 vaginal hysterectomies (study group) were compared with 59 abdominal hysterectomies (control group); all of the hysterectomies were performed for symptomatic uterine fibroids from January 1997 through December 2000. We excluded from the study the other common causes of hysterectomy such as prolapse, bleeding, adenomyosis, and endometrial or cervical carcinoma. In both groups, uterine weights ranged from 200 g to 1300 g. For enlarged uteri, vaginal hysterectomies were performed with the use of volume reduction techniques: Intramyometrial coring, corporal bisection, and morcellation. The evaluated parameters included patient age, weight, parity, uterine weight, operative time, blood loss, demand for analgesics, eventual surgical complications, length of admission, and hospital charges. The Mann-Whitney U test and chi(2) tests were applied for statistical analysis. Probability values of <.05 were considered statistically significant. RESULTS: There were no major differences in patient age, weight, parity, and uterine weight between the two groups. Operative time was significantly lower for the vaginal route as compared with the abdominal route (86 minutes vs 102 minutes, P <.001). No intraoperative complications were noted both in the study and control groups or the control group. Surgical bleeding (expressed by hemoglobin loss) was not significantly different between the two groups. In the postoperative period, we found a higher incidence of fever (30.5% vs 16.6%, P <.05) and demand for analgesics (86% vs 66%, P <.05) in the abdominal group as compared with the vaginal group. Significant advantages of vaginal hysterectomy were a reduction in the hospital stay (3 days vs 4 days, P <.001) and cost. CONCLUSION: These results should lead to the choice of vaginal hysterectomy as a valid alternative to the abdominal hysterectomy, even for enlarged uteri.
Adult↗
Risk of genital prolapse and urinary incontinence due to pregnancy and delivery. A prospective study.
BACKGROUND: Recent literature shows conflicting results regarding this subject. Using a prospective study, we analysed the possible effects of pregnancy and delivery upon the pelvic floor support. METHODS: In a group of 344 patients who received our phone-call 3 months after delivery, only 58 accepted the investigation, and came for an exam. We looked out for pathologies such as genital prolapse and stress urinary incontinence (IUS). During the exam we analysed: vagino-perineal scars; descensus of the vaginal walls and of the uterus; dyspareunia; urinary frequency and urgency; urge Incontinence and IUS; weakening of pelvic floor muscles. RESULTS: We objectively identified in cystocele the prevalent "anatomic" damage, and in IUS, the most frequent "functional" damage. We then tried to find a statistical correlation between these pathologies and the most important risk factors cited in the literature. CONCLUSIONS: Through the systematic analysis of the obtained data, we thus identified the most important risk factors that lead to the development of these pathologies: operative delivery, pluriparity, heavy work, high BMI in mothers and newborns. The results that emerged from our study lead to some remarks of interest and discussion.
Data Interpretation, Statistical↗
Chemically assisted dissection of tissues: an interesting support in abdominal myomectomy.
BACKGROUND: The aim of this study was to verify the efficacy of sodium-2-mercaptoethanesulfonate (mesna) in the chemical separation of tissues in abdominal myomectomies when used with the traditional mechanical separation techniques. STUDY DESIGN: In a prospective, randomized study, 58 women underwent abdominal myomectomy. In 29 of these, we used mesna for highlighting and separating tissues, and in the other 29 we used saline solution for the same purposes. The variables evaluated included the number of myomas removed, the volume of the biggest myoma, and the total volume of the myomas removed in every intervention. We also recorded operating time, the length of hospital stay, the degree of procedure difficulty, perioperative blood loss, operative complications, and cost. RESULTS: The operation was significantly shorter in the mesna group (p < 0.05) even though the volume and the number of myomas were larger. The degree of difficulty evaluated by the surgeon at the end of every operation was not significantly different in the two groups. The reduction in hemoglobin 24 hours after operation was significantly less in the patients treated with mesna (p = 0.006), but this difference was probably altered by the increase in hematocrit levels. CONCLUSIONS: Because of its ability as a chemical dissector, mesna may be a useful aid in this type of benign gynecologic operation. Larger studies to confirm this are needed.
Adult↗
Trends of spontaneous abortions in Italy 1990-1995.
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Abortion, Spontaneous↗
Ceramide 2 (N-acetyl sphingosine) is associated with reduction in Bcl-2 protein levels by Western blotting and with apoptosis in cultured human keratinocytes.
BACKGROUND: Ceramides produced by sphingomyelin hydrolysis activate a cycle that is followed by three different major cellular responses: downregulation of cell proliferation, induction of cell differentiation and apoptosis. In the skin, the generation of intracellular ceramide may also provide a link between an extracellular signal and the induction of the apoptosis programme for the elimination of damaged cells. OBJECTIVES: We investigated the effect of ceramides capable of entering cells on cultured keratinocytes. METHODS: Human keratinocytes from neonatal skin were cultured in serum-free medium with or without increasing concentrations of ceramide 2 (CER-2; N-acetyl sphingosine) (5, 10, 20 and 40 micromol L-1). Proliferative effects were studied either by cell counts or by 3H-thymidine incorporation and flow cytometric analysis. Apoptosis was studied by TUNEL staining and Western blot analysis of Bcl-2 protein. RESULTS: Cell counts and DNA synthesis were reduced in a dose-dependent manner following CER-2 treatment. TUNEL staining showed CER-2-induced apoptosis at 48, 72 and 96 h. Western blot analysis showed that CER-2 induces downregulation of Bcl-2 at 24-96 h. CONCLUSIONS: These results demonstrate that CER-2 inhibits cell proliferation and induces apoptosis, possibly via a Bcl-2-dependent mechanism.
Apoptosis↗
[Perinatal morbidity and mortality in children born to mothers with gestational hypertension].
Gestational hypertension is a severe pathology leading to important maternal and neonatal effects. It represents one of the most important causes of maternal morbidity and contributes to a high percentage of perinatal mortality, determined by fetal hypoxia and especially by prematurity and low birth weight. To-date the only treatment offered in gestational hypertension remains delivery, which has to be scheduled regarding timing and method on the basis of the appearance of hypertension, of its severeness and maternal and fetal complications. To evaluate the clinical course and the presence of hypertensive risk factors, a clinical-epidemiological study was carried out on two groups of pregnant women: a group made up of 50 women with hypertension and a control group of 80 women in whom no gravidic pathology arose. We hence were able to reveal the risk factors associated with hypertension in pregnancy such as maternal age, nulliparity, and elevated body mass index. Regarding neonatal prognosis, we observed a higher incidence in premature birth (30th- to 38th week of gestational age) and the need for elective or urgent caesarean sections, with respect to the spontaneous deliveries observed in the control group. We also observed reduced weight of both placenta and the newborn in hypertensive mothers with significant statistical differences between the two groups (p < 0.001). Evaluation of neonatal data at birth showed lower Apgar indices at 1st and 5th minute from birth in the study group with a higher percentage of newborns transferred to the neonatal intensive care unit. We also observed a high percentage of still-births equal to 14% in the study group as opposed to the control group.
Adult↗
[Evaluation of the peripartum effects of 2 analgesics: meperidine and tramadol, used in labor].
The need for analgesia to overcome pain in labour is highly requested by women today. Various ways either non pharmachologic e.g. Emotional sustain, psycho-prophylactic preparation, yoga and hypnosis or pharmachologic such as epidural blockade or parenteral are used. Therefore in our study we evaluated the efficacy and tolerability of the two opioids usually used today in parenteral analgesia to reduce pain during labour: Tramadol and Meperidine. We studied two groups of patients each made up of 20 women in labour, all at term and with a physiologic course of pregnancy. 75 mg i.m. of Meperidine chloryhydrate were somministered in the first group while in the second group 100 mg i.m. of tramadol chloryhydrate were somministered. Various maternal, fetal and neonatal parameters were then monitored demonstrating--A moderate maternal analgesic effect in both drugs (evaluated through the analogic grading of pain). In the group to whom Meperidine was given, sedative effects on the mother were observed associated with respiratory depression in the newborn (the latter evaluated through the Apgar index at 1st and 5th minute of life and pH of the blood obtained at the umbilical cord. The data obtained permitted us to conclude that Tramadol in accordance to the obtained in literature gives an analogous analgesic effect, with better tolerability for the absence of collateral effects on the mother, fetus and newborn.
Analgesia, Obstetrical↗
[Lavage of the birth canal with chlorhexidine: a new valid method for the prevention of perinatal infections].
Perinatal morbidity and mortality are due to various infective agents, mainly represented by beta-hemolytic group B Streptococcus. The perinatal disease related to this infection is distinguished in Early-onset, characterised by pneumonia and sepsis, and Late-onset which leads to sepsis, meningitis and pneumonia. Various strategies were therefore proposed to prevent transmission including immunisation and chemoprophylaxis. All these methods however present adverse effects and are most of all expensive to carry out. Taha et al. reported an interesting experience regarding the reduction of perinatal infections following the cleansing of the birth canal with a solution of Chlorhexidine 0.25% during labour (1996-1997). It seemed interesting for us to assess the applicability and efficacy of a new strategy of prophylaxis of perinatal infections in a Developing Country based on the association of two of the simple strategies proposed i.e.: cleansing the birth canal with chlorhexidine and chemoprophylaxis in cases with risk factors without culture screening. We studied two groups of patients: one in which cleansing of the birth canal was used and the second (control group) in which the old method already applied in the hospital (i.e. cleansing of the external genitals with Cetrimide 1%+ Chlorhexidine 0.1%) was carried out associated with antibiotic therapy when risk factors arose. We observed a total absence of neonatal mortality due to sepsis resulting from the association of the methods suggested even though the presence of sepsis evaluated through signs and symptoms like fever, poor feeding, apnoea or dyspnoea in newborns was similar in both groups.
Chlorhexidine↗
In vitro testing of tensides employing monolayer cultures: a comparison with results of patch tests on human volunteers.
Evaluation of the irritant potential of new products or ingredients prior to human testing is generally performed in vivo on animals. However, according to the 6th amendment and following updates of the European Community directive on cosmetic products (93/35/EEC), animal testing will be banned when suitable substitutes will be available. To know whether in vitro tests for assessment of skin irritancy provide results approaching human conditions, comparisons have to be made between data deriving from in vitro tests and skin response in humans. The aim of our study was to assess the validity of the monolayer culture system of normal human keratinocytes as a model for the evaluation of the irritant effects of detergents, by comparing in vitro cell culture data to in vivo acute skin irritancy effects of cocamidopropyl betaine (CAPB), an amphoteric compound, Tween 20 (TW20) (polysorbate 20) and Tween 80 (TW80) (polysorbate 80), representing nonionic compounds, applied to the skin of 24 healthy volunteers at a concentration similar to that employed in commercial products. As parameters for cytotoxicity, cell proliferation, cell membrane integrity and cell metabolism were assessed by cell counts, thymidine incorporation, MTT conversion, and Neutral Red uptake. In order to increase the sensitivity of the in vivo evaluation, bioengineering methods for assessment of the effects of test products on the skin were employed. Whereas all 4 in vitro methods ranked the tensides according to their toxicity in the following order: CAPB>SLS>TW20>TW80, both in vivo methods agreed in identifying SLS as the most irritating substance. Moreover, as compared with the irritation potential on human skin, all 4 in vitro tests overestimated the toxicity of CAPB. This suggests that the keratinocyte monolayer cell culture technique cannot directly replace in vivo methods, and that data obtained by this method should be interpreted cautiously.
Adolescent↗
1,25-dihydroxyvitamin D3, transforming growth factor beta1, calcium, and ultraviolet B radiation induce apoptosis in cultured human keratinocytes.
Apoptosis is a cellular process of self-directed suicide that plays a key role during morphogenesis and in the maintenance of homeostasis in continuously renewing tissues. Currently, apoptosis is detected mainly by gel electrophoresis of fragmented DNA and by typical ultrastructural features such as cell shrinkage and chromatin condensation. Recently, an in situ technique was developed that allows the detection of the apoptotic process in cells and the quantitation of apoptosis in cell populations. We applied this technique to evaluate the apoptotic process in cultured normal human keratinocytes under basic conditions and after stimulation with factors and agents that are presumed but have never been proved to induce apoptosis in these cells. Apoptosis was analyzed after stimulation with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], transforming growth factor beta1 (TGFbeta1), calcium, UVB, or tumor necrosis factor alpha (TNFalpha). All these factors except TNFalpha induced apoptosis in human keratinocytes. Whereas UVB and calcium were good apoptogenic stimuli at 6 and 24 h, respectively, the vitamin D derivative and TGFbeta1 induced apoptosis after 5 and 6 d in culture. Apoptosis was also established by DNA fragmentation and electron microscopy. Finally, TUNEL technique showed that the number of apoptotic cells increases slightly (5-10%) from 24 to 144 h even in untreated keratinocytes. Our studies indicate that factors normally involved in the regulation of cell growth and differentiation can also control apoptosis.
Apoptosis↗
Autocrine nerve growth factor protects human keratinocytes from apoptosis through its high affinity receptor (TRK): a role for BCL-2.
Normal human keratinocytes synthesize and release nerve growth factor (NGF) and express both the low- and the high-affinity NGF receptor. Because NGF has been shown to rescue certain cell types from programmed cell death, we investigated the role of endogenous NGF in preventing keratinocyte apoptosis. We report here that apoptosis is induced in normal human keratinocytes in culture by blocking endogenous NGF signaling with either anti-NGF neutralizing antibody or K252, a specific inhibitor of the tyrosine kinase high-affinity NGF receptor. Apoptosis was assessed by DNA laddering, electron microscopy, and in situ nick end labeling technique. In anti-NGF-treated keratinocytes, the apoptotic process starts at 96 h, and is maximal at 120 h. After K252 treatment, apoptosis starts at 48 h and peaks at 120 h. Because the product of the bcl-2 proto-oncogene protects many cell types from apoptosis, we measured the levels of this protein in apoptotic keratinocytes. We found that both K252 and anti-NGF antibody strikingly downregulate bcl-2 expression, starting at 72 h. Furthermore, HaCat keratinocytes stably transfected with a plasmid containing bcl-2 cDNA fail to undergo apoptosis when treated with K252. These findings show that autocrine NGF acts as a survival factor for human keratinocytes in vitro through its high-affinity NGF receptor, possibly by maintaining constant levels of Bcl-2.
Apoptosis↗
Nerve growth factor receptor and neurochemical markers in human oral mucosa: an immunohistochemical study.
BACKGROUND: The innervation of the oral mucosa has so far been studied mainly by histochemical and ultrastructural techniques. Only few studies have investigated the presence of neural proteins and neurotransmitters in human gingival mucosa. OBJECTIVE: The purpose of the present study was to evaluate the presence and distribution of neural structural and transmitter proteins in different areas of normal human oral mucosa. METHOD: Indirect immunofluorescence was employed on specimens taken from different mucosal regions (gingiva, lips, gums, palate). Both structural (low-affinity nerve growth factor receptor, NGFr; protein gene product 9.5, PGP 9.5) and neuropeptide markers (substance P; calcitonin gene-related peptide; vasoactive intestinal peptide, neuropeptide Y) were used. RESULTS: NGFr and PGP 9.5 intensely labelled both nerve fibres and selected epithelial cells, while neuropeptide immunoreactivity was scarcely expressed and exclusively localized in nerve fibres. CONCLUSIONS: Similarly in the distribution pattern and neurochemistry between oral and cutaneous innervation is apparent. Expression of NGFr could be relevant to the trophism of both the oral innervation and epithelium.
Adolescent↗
An attempt at real prophylaxis of primary dysmenorrhea: comparison between meclofenamate sodium and naproxen sodium.
Dysmenorrhea is a widespread phenomenon, affecting mainly young nulliparous women, often inducing difficulties in study or in work. Its pathogenesis involves a release of local vasoconstrictors like Prostaglandins and Leukotrienes. Modern therapy is based firstly on the administration of prostaglandin-Synthetase Inhibitors or Contraceptive Pills, with the aim of reducing the menstrual excess of pain inducing substances. In order to achieve more efficacy, on the basis of the already proven effectiveness of the Non Steroid Anti-Inflammatory Drugs (NSAID)s in this field, we recently set out to prevent dysmenorrhea in a double-blind randomized study with Meclofenamate Sorium and Naproxen Sodium. Through the observation of the drop in Basal Body Temperature which usually precedes menstrual flow, we were able to instruct our patients in the earlier recognition of impending menstrual onset, leading to earlier prevention of Prostaglandin and Leukotriene release. Meclofenamate Sodium in particular led to considerable pain reduction, with very good patient compliance and without significant complications, probably of its additional receptor effect.
Adolescent↗
Substance P is diminished and vasoactive intestinal peptide is augmented in psoriatic lesions and these peptides exert disparate effects on the proliferation of cultured human keratinocytes.
An involvement of neurogenic components in the pathogenesis of psoriatic lesions has been suggested and neuropeptides are thought to play a modulatory role in cutaneous inflammation. In this study, we evaluated the immunoreactivity of the neuropeptides vasoactive intestinal polypeptide (VIP) and substance P (SP) in the skin of patients with chronic plaque psoriasis, by immunohistochemistry and radioimmunoassay. No differences were observed, by immunohistochemistry, in the expression and localization of VIP and SP between psoriatic and normal skin. Using the radioimmunologic technique on whole skin homogenates, VIP levels were significantly increased in psoriatic lesions as compared to normal skin. By contrast, SP levels were significantly lower in lesional and non-lesional psoriatic skin than in normal skin. In addition, we examined the effect of VIP and SP on the proliferation of cultured normal human keratinocytes. VIP (1-28) (1 nM-1 microM) as well as VIP fragments (10-28) (1 nM-1 microM) and (22-28) (1 nM-1 microM) stimulated the proliferation of keratinocytes in a dose-dependent manner, whereas the VIP fragment (1-12) (1 nM-1 microM) was ineffective. The VIP antagonist (N-Ac-Tyr1, D-Phe2)-GRF (1-29)-NH2 (0.1 microM) significantly inhibited the VIP effect on keratinocytes. On the other hand, SP (0.1 microM) not only failed to stimulate keratinocyte growth, but also blocked the VIP-induced stimulation of these cells. The imbalance of cutaneous VIP and SP and their disparate effects on the proliferation of normal human keratinocytes in culture would suggest that these peptides are involved in the pathogenesis of psoriasis and may exert different modulatory activities in the mechanisms underlying the psoriatic lesion.
Cell Division↗
Effectiveness of magnesium pidolate in the prophylactic treatment of primary dysmenorrhea.
To evaluate Magnesium (Mg) effectiveness in the treatment of primary dysmenorrhea, 30 volunteer dysmenorrheic women of mean age 22.6 years were selected from the out-patients of the Dept. of Obstetrics and Gynaecology of the University of Parma during the period January-December 1989. Patients affected by secondary dysmenorrhea were excluded from the trial. The women considered were asked to self-evaluate their menstrual pain for 6 subsequent cycles using the VAS (Visual Analogue Scale). In the first cycle, as control, no drug was administered; in the following ones, every woman was given 4.5 mg oral Mg Pidolate in 3 administrations daily, from the 7th day preceding the onset of menses till the 3rd day of menstruation. Data were statistically analyzed. In Mg-treated cycles compared with the control one, first day dysmenorrhea progressively decreased, with a significant drop (p < 0.05) from the 1st to the 6th cycle. A similar trend, but not statistically significant, was seen for the 2nd and 3rd day of cycle. No side effect was remarked. These data suggest Mg administration to be a reliable therapy of primary dysmenorrhea.
Adult↗
Glucose tolerance and insulin release in adolescent female.
The increase in insulin requirement at the onset of adolescence is compensated by an increase of insulin secretion. This metabolic pattern persists during adolescence but is no longer present in adults. It is supposed to depend on a decrease of insulin sensitivity of uncertain origin. We compared the metabolic pattern of late adolescent girls (13-16 year old) with young women (21-30 year old) with similar body mass indexes, testing subjects with iv glucose tolerance test (IVGTT) (glucose 0.33 g/kg) and arginine test (ATT) (arginine 30 g in 30 min). In late adolescent vs adult women we observed: i) IVTT: similar k of glucose tolerance and higher insulin and C-peptide responses; ii) ATT: unmodified plasma glucose, insulin and glucagon values, higher GH plasma levels; iii) in adolescent girls GH and CPR incremental areas significantly correlated (r = 0.755, p less than 0.05). These data show that: i) the adolescent pattern of glucose metabolism persists after completion of sexual development and, ii) there is a positive correlation between GH response to arginine and beta-cell response to glucose. So GH should play a role in the impairment of glucose metabolism during adolescence.
Adolescent↗