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Biomedical subjects

C Benedetto

Publications and source records attributed to C Benedetto.

At least 73 records · Page 4Linked to original sources

Corticotropin-releasing hormone increases prostaglandin F2 alpha activity on human myometrium in vitro.

OBJECTIVE: Our purpose was to study the capability of synthetic corticotropin-releasing hormone to directly stimulate human myometrium and to modulate the activity of prostaglandins F2 alpha and E2. STUDY DESIGN: Strips from human myometrium were obtained from 127 elective cesarean sections at term. The in vitro effect of human rat corticotropin-releasing hormone on myometrial contractility has been studied in resting myometrial strips mounted in a two-chamber bath for isolated organs. Stimuli (corticotropin-releasing hormone, prostaglandins F2 alpha and E2, and oxytocin) were administered as one single dose in the perfusion chamber. In each experiment one myometrial strip was used as a control. RESULTS: Corticotropin-releasing hormone significantly increases (p < 0.01) the myometrial response to prostaglandin F2 alpha. The hormone neither has a direct inotropic effect nor is it able to enhance the effect of prostaglandin E2 and oxytocin on myometrial strips. CONCLUSION: The positive effect of corticotropin-releasing hormone on the myometrial response to prostaglandin F2 alpha adds new support to the theory that placental corticotropins may modulate the onset of labor.

Corticotropin-Releasing Hormone↗

Immunolike growth hormone substance in tissues from human embryos/fetuses and adults.

GH immunolike reactivity was measured by RIA and IRMA tests in the extracts of tissues from human fetuses (8-32 weeks) and adults. For some fetal tissues a comparison was made with the T4 values obtained in a previous study. Both hormones were already measurable in peripheral tissues at 8 weeks of gestation. The increase in GH was faster than for T4 and it reached the zenith at approximately 20 weeks; thereafter, the GH concentration declined until delivery. In contrast, T4 progressively increased until term. Thirteen tissues were studied both in fetuses and in adults: the GH concentration was about 10 times higher in fetal tissues, with the exception of the brain and the pancreas. The brain showed the lowest GH concentration throughout fetal life and adulthood, whereas the highest GH levels were recorded in adults' pancreas, but they resulted to be artifacts since the RIA values were not confirmed by the IRMA test. In both groups of subjects the highest GH concentrations were found in kidneys, liver and small intestine; the lowest, beyond the brain, in red muscle and cartilage. Thus, the pattern of the quantitative distribution of GH in fetal tissues is the same as in adults, suggesting a functional role of the hormone in the developing human during the prenatal period, in contrast with the concept that high tissue levels of GH are a mere reflection of high GH blood levels. Moreover, in all tissues examined no correlation was found between GH and T4 concentration.

Adult↗

[Pre-menopausal dysfunctional menometrorrhagia: therapeutic approach].

Approximately 10% of premenopausal women suffer from dysfunctional menometrorrhagia. The correct therapeutic approach to this pathology above all requires a precise diagnostic framework. For this purpose the doctor can employ a number of laboratory and instrumental tests, both invasive and non-invasive, in order to differentiate the dysfunctional forms from those supported by organic pathologies or non-gynecological diseases. Once the diagnostic iter has been completed, the choice of therapy can be directed towards surgical or medical treatment; the latter may be symptomatic or causal. This review focuses on the most commonly used treatments for dysfunctional menometrorrhagia in premenopausal women and proposes clinical protocols for a correct diagnostic and therapeutic approach.

Endocrine System Diseases↗

Increased activity of 6-phosphogluconate dehydrogenase and glucose-6-phosphate dehydrogenase in purified cell suspensions and single cells from the uterine cervix in cervical intraepithelial neoplasia.

The activities of 6-phosphogluconate dehydrogenase and glucose-6-phosphate dehydrogenase have been measured in squamous epithelial cells of the uterine cervix from normal patients and cases of cervical intraepithelial neoplasia (CIN). A biochemical cycling method, which uses only simple equipment and is suited to routine use and to automation, was applied to cells separated by gradient centrifugation. In addition, cells were examined cytochemically, and the intensity of staining in the cytoplasm of single whole cells was measured using computerised microcytospectrophotometry. Twenty per cent of cells in samples from normal patients (n=61) showed staining intensities above an extinction of 0.15 at 540 nm, compared to 71% of cases of CIN 1 (n=14), 91% of cases of CIN 2 (n=11) and 67% of cases of CIN 3 (n=15). The cytochemical data do not allow definitive distinctions to be made between different grades of CIN whereas the biochemical assay applied to cell lysates shows convincing differences between normal samples and cases of CIN. There are no false negatives for CIN 3 (n=14) and CIN 2 (n=10) and 11% false negatives for CIN 1 (n=9) and 14% of false positives for normal cases (n=21). The results of this preliminary study with reference to automation are discussed [corrected].

Cell Separation↗

Repeated albumin infusions do not lower blood pressure in preeclampsia.

Since intravascular volume contraction is regarded as an important pathological feature in preeclampsia, it has been proposed that plasma volume expansion could be a therapeutic manoeuver that interrupts the pathogenetic chain of hypovolemia inducing increased vascular resistance. Furthermore, tissue perfusion should be improved and, if albumin is used as plasma expander agent, interstitial edema should also be reduced. We report the results observed in an open pilot study in ten preeclamptic patients treated with daily albumin infusions (0.4 to 1 g/kg) from 7 to 36 days. No acute effects were shown on blood pressure, and the need for antihypertensive therapies did not decrease in the following days. Serial evaluation after at least five or ten days of repeated albumin infusions did not show stable changes in electrolytes excretion, renal clearances, serum protein concentration and hematocrit value, nor in aldosterone, renin and atrial natriuretic peptide basal levels, while proteinuria tended to increase. Uteroplacental and fetoplacental blood flow acutely ameliorated in 3 cases only after albumin 1 g/Kg, but reached basal values again on the next day. The clinical implications are that daily albumin infusions with this schedule dosage do not lower blood pressure and that they are unable to induce stable changes in renal function, uteroplacental and fetoplacental resistance. No maternal complications were observed during the conservative management, but fetal mortality was high (6/10). Given the uncontrolled study, we cannot know whether similar results had been achieved by conventional therapy only.

Adult↗

Increased concentrations of eicosanoids and platelet-activating factor in menstrual blood from women with primary dysmenorrhea.

Prostanoids, leukotrienes and platelet-activating factor were measured by radioimmunoassay in menstrual blood of seven women with primary dysmenorrhea and five healthy controls. The eicosanoids and PAF concentrations in dysmenorrheic patients were significantly higher than those found in healthy women (P less than 0.005 for PGF2 alpha, 11-dehydro-TXB2, 2,3-dinor-TXB2 and LTC4/D4; P less than 0.001 for PAE; P less than 0.05 for PGE2 and 2,3-dinor-6-keto-PGF1 alpha). Whereas no relationship could be found between the concentrations of PGF2 alpha, PGE2, 11-dehydro- and 2,3-dinor-TXB2 and severity of primary dysmenorrhea, a close correlation between LTC4/D4 and PAF and severity of the disease was observed, particularly in patients who responded poorly to therapy with prostaglandin synthetase inhibitors. We conclude that the hyperstimulation of myometrial activity is not caused by selective stimulation of one metabolic pathway of arachidonic acid, but rather by an overall stimulation of phospholipid metabolism. The assessment of prostanoids, leukotrienes and PAF in menstrual blood many be useful as a direct index of primary dysmenorrhea, and the development of their antagonists may have therapeutic implications in improved treatment of the disease.

Adult↗

Quantitative measurements of the changes in protein thiols in cervical intraepithelial neoplasia and in carcinoma of the human uterine cervix provide evidence for the existence of a biochemical field effect.

Quantitative micromethods have been used for measuring reactive protein thiols (PSHr), total reactive protein sulfur (TRPS), total protein thiols (PSHt), and protein disulfides (PDS) in fixed frozen sections of human uterine cervix. PSHr and TRPS were stained using 2,2'-dihydroxy-6,6'-dinaphthyl disulfide; PSHt and PDS were stained using mercurochrome methods. Microspectrophotometric measurements were made on the stained sections using a microdensitometer with associated data processing; the results obtained for areas of epithelium and stroma were converted to absorbance values per micron 2. Samples of uterine cervix that were diagnosed as containing cervical intraepithelial neoplasia (CIN) I-III or carcinoma were examined and compared with samples of normal uterine cervix. Measurements were made not only on identified lesions but also on apparently normal tissue obtained from the same cervix. Epithelial/stroma ratios (E/S) were calculated for PSHr, TRPS, PSHt and PSHt + PDS; in addition, the double ratios of PSHr/TRPS and PSHt/PSHt + PDS were also calculated for E/S. The mean E/S values for PSHr and PSHt were significantly different for all types of lesion compared with control samples. The E/S ratios for apparently normal tissue obtained from cervices with CIN or carcinoma were also significantly different compared with corresponding control values, indicating a field effect. There was a considerable degree of overlap between individual values in the control groups versus those obtained with each type of lesion. The corresponding mean E/S values for TRPS and for PSHt + PDS in the samples containing lesions were not significantly different from control means except for the group containing CaCx. However, the mean values for the double ratios (PSHr/TRPS and PSHt/PSHt + PDS) were significantly different in the groups containing lesions compared with the controls. Moreover, apparently normal tissue obtained from cervices containing CIN or carcinoma had different mean values compared with the controls, confirming the existence of a field effect. The degree of overlap of individual values in the lesion groups compared with the control values was much less with double ratio values than previously noted for single ratio values. In consequence, the double ratio measurements clearly discriminated CIN I + II and CIN-III from controls. Our data show that CIN is associated with marked changes in tissue protein thiols and disulfides and that these differences extend to neighboring apparently normal tissue indicative of a field effect.

Adult↗

Studies on the hyperplasia ('regeneration') of the rat liver following partial hepatectomy. Changes in lipid peroxidation and general biochemical aspects.

Using the experimental model of partial hepatectomy in the rat, we have examined the relationship between cell division and lipid peroxidation activity. In rats entrained to a regime of 12 h light/12 h dark and with a fixed 8 h feeding period in the dark phase, partial hepatectomy is followed by a rapid regeneration of liver mass with cycles of synchronized cell division at 24 h intervals. The latter phenomenon is indicated in this study by pulses of thymidine kinase activity having maxima at 24 h, 48 h and 72 h after partial hepatectomy. Microsomes prepared from regenerating livers show changes in lipid peroxidation activity (induced by NADPH/ADP/iron or by ascorbate/iron), which is significantly decreased relative to that in microsomes from sham-operated controls, again at 24 h, 48 h and 72 h after the operation. This phenomenon has been investigated with regard to possible underlying changes in the content of microsomal fatty acids, the microsomal enzymes NADPH:cytochrome c reductase and cytochrome P-450, and the physiological microsomal antioxidant alpha-tocopherol. The cycles of decreased lipid peroxidation activity are apparently due, at least in part, to changes in microsomal alpha-tocopherol content that are closely associated in time with thymidine kinase activity.

Animals↗

Histophotometry of protein thiols and disulphides in tissue samples from the human uterine cervix and the skin reveals a "field effect" as well as an "extended field effect" of malignant tumours.

Fresh frozen and fixed serial sections were stained with 2,2'-dihydroxy-6,6'-dinaphthyldisulfide (DDD) and Fast blue B for reactive protein thiols (PSHr) and total reactive protein sulfur (TRPS). The mean optical densities of PSHr and TRPS determined histophotometrically at a distinct part of a tissue were related to each other (PSHr: TRPS). If this quotient has been determined, e.g. for normal epithelium and the adjacent stroma, both quotients can be related to each other by a double quotient (Q PSHr: TRPS). With the aid of the double quotient highly significant differences could be found between tumours and normal tissue from patients without tumour of the human uterine cervix. Similar differences exist between normal skin from healthy patients and skin tumours. Q PSHr: TRPS revealed similar differences to exist between normal tissue of patients without tumour and apparently normal tissue in the neighbourhood of tumours of the uterine cervix and of skin ("field effect" of tumours). Histophotometric investigations on abdominal skin (and skin of breast) showed highly significant differences between normal skin of patients without tumour and patients with various kinds of tumours of the uterine cervix, ovaries, liver and breast ("extended field effect" of tumours).

Cervix Uteri↗

Deep femoral lymphadenectomy with preservation of the fascia lata. Preliminary report on 42 invasive vulvar carcinomas.

Forty-two patients with primary invasive vulvar carcinoma were treated with radical vulvectomy and deep femoral lymphadenectomy with preservation of the fascia lata and cribriform fascia. The rationale for using this technique was based on anatomic knowledge of the topographic distribution of groin lymph nodes, which was confirmed by the study of 50 cadavers. The preliminary data show that the number of superficial and deep femoral lymph nodes removed from the 42 patients (mean number of nodes, 20; range, 8-32) was similar to the number reported in anatomy books. In addition, the five-year actuarial survival rate, 70%, was comparable to that in the literature. These preliminary results suggest that the surgical technique used in this study is as radical an oncologic procedure as Way's classic groin lymphadenectomy, which consists of removing the fascia lata and cribriform fascia.

Aged↗

Reduced serum inhibition of platelet-activating factor activity in preeclampsia.

We determined in normal nonpregnant (group 1) women, normal pregnant (group 2) women, and patients with preeclampsia (group 3) the serum inhibition of platelet-activating factor activity, the presence of detectable amounts of platelet-activating factor in the blood, and platelet responsiveness in vitro to platelet-activating factor, and to other agonists (adenosine diphosphate, collagen, and ristocetin), and prostacyclin (prostaglandin I2). In patients with preeclampsia (group 3) the serum inhibition of platelet-activating factor activity was significantly lower than that in groups 1 and 2. However, no detectable amounts of platelet-activating factor were observed. The mean values of platelet aggregation induced by platelet-activating factor, adenosine diphosphate, collagen and ristocetin, and the prostaglandin I2-inhibitory concentration of 50% which is inversely correlated with platelet sensitivity to prostaglandin I2, were not significantly different between groups 2 and 3. It is suggested that in preeclampsia the defect in serum inhibitory potential of platelet-activating factor--induced platelet aggregation may contribute to the disturbance in the homeostatic balance between proaggregant and antiaggregant substances.

Adenosine Diphosphate↗

Relevance of prostaglandins in true menstrual migraine.

Eighteen patients suffering from true menstrual migraine and 12 control subjects were studied. We evaluated in different phases of the menstrual cycle and during the migraine crisis the peripheral plasma concentrations of 6-keto-PGF1 alpha (the stable metabolite of PGI2), thromboxane B2 (the stable metabolite of thromboxane A2), PGF2 alpha and PGE2. The mean values of 6-keto-PGF1 alpha in menstrual migraine sufferers are lower than in normal women throughout the whole cycle. The difference between the trends observed in the two groups is statistically significant (p less than 0.05). The plasma levels of TXB2 and of PGF2 alpha are similar in the two groups investigated, both in basal conditions and during the attack. The plasma concentrations of PGE2 are slightly lower in migraineurs in basal conditions than in normals. However, during the crisis they increase significantly (p less than 0.05). In conclusion, among all the parameters considered, PGE2 seems to play the most important role during the pain phase of the attack. The results of the present study suggest that a deficit of PGI2, one of the most important protecting agents against ischemia, might be a typical feature of menstrual migraine and might cause in these patients a vascular hypersensitivity to different ischemic stimuli.

6-Ketoprostaglandin F1 alpha↗

Eicosanoids in primary dysmenorrhea, endometriosis and menstrual migraine.

This paper summarizes what has been learned over the years about the role of eicosanoids in the pathogenesis of primary dysmenorrhea, endometriosis and menstrual migraine. The role of prostaglandins (PGs) in the pathogenesis of primary dysmenorrhea is inferred from four main observations: firstly, the clinical symptoms of primary dysmenorrhea are similar to those induced by the administration of PGF2 alpha and PGE2 for the induction of labour; secondly, the increased production of PGs by the endometrium during the luteal and menstrual phases of ovulatory cycles is consistent with the occurrence of primary dysmenorrhea mainly in ovulatory cycles; thirdly, the concentrations of PGF2 alpha and PGE2 in the endometrium and menstrual fluid of dysmenorrheic women are significantly higher than in controls; fourthly, certain PG inhibitors have been proved to be effective in the treatment of dysmenorrhea. The change in PG production can explain the major symptoms of primary dysmenorrhea, including the increased uterine contractility, uterine ischemia and the lowering of the pain threshold to chemical and physical stimuli in the pelvic nerve terminals. Moreover, recent experimental data suggest that leukotrienes (LTs) might be among the alternative pathogenetic causes of primary dysmenorrhea. The data which support a relationship between eicosanoids and endometriosis are as follows: endometriotic tissue produces PGs; the peritoneal fluid concentration of PGF2 alpha increases significantly after the induction of endometriosis in laboratory animals; the concentration of PGs in peritoneal fluid of some patients with endometriosis is greater than in controls and, finally, the number and activation of pelvic macrophages which are able to synthesize eicosanoids increase in patients with endometriosis. Possible roles for eicosanoids in the pathogenesis of infertility and secondary dysmenorrhea induced by endometriosis have been suggested. Eicosanoids are probably also involved in the pathogenesis of menstrual migraine. Different types of PGs might play a role both in the initial vasoconstriction during the prodromal phase of migraine and in the vasodilation and sensitization to pain typical of the pain phase.

Dysmenorrhea↗

Histophotometric quantification of the field effect and the extended field effect of tumors.

Histophotometric investigations have been made on samples of human skin. Fresh frozen serial sections were fixed and stained for either reactive protein thiols (PSHr) or total reactive protein sulphur (TRPS) using modifications of the DDD-Fast blue B-method. In addition, total protein thiols (PSHt) were stained with the Mercurochromcyanide-method, and proteins were stained using a modified amido-black procedure. Significant differences were found between the different tumours investigated and normal tissue, and also between apparently normal tissue adjacent to the tumours and normal tissue from patients without tumour. To reveal such tumour-related changes of apparently normal tissue, termed the field effect of tumours, a double quotient had to be calculated from the PSHr-and TRPS-values determined from both epithelium (epidermis) and connective tissue. In addition, abdominal skin was investigated from patients without tumour and patients with tumours of the female genital tract, liver or breast. With the aid of the double quotient procedure, highly significant differences were found between normal abdominal skin of patients without tumours versus similar samples taken from patients with tumours. The tumour-related changes found with abdominal skin distant from the tumours have been termed the extended field effect of tumours. These general tumour-related changes, independent of the size, state or degree of malignancy of the distant tumour, could be shown to be due to changes in abdominal dermis.

Female↗

Adrenocorticotropic hormone and catecholamines in maternal, umbilical and neonatal plasma in relation to vaginal delivery.

The aim of this study was to evaluate the effect of vaginal delivery on both ACTH and catecholamines (DA, NE, E) secretion in the mother, the fetus (umbilical artery) and the newborn. Blood samples were obtained from 19 normal pregnant women and the corresponding umbilical cords, and from the newborns. Seventeen normal nonpregnant women, matched for age and parity, were also included in the study as "nonpregnant controls". The results demonstrate that in the mother, plasma catecholamines (CA) concentrations during labor and delivery are elevated above the values reported for normal nonpregnant women and there is a predominant E response. The concentrations of CA in umbilical arteries are very high compared to those in the corresponding mother and they fall rapidly after birth. Unlike that in the mother, the predominant CA response to parturition in the fetus and newborn infant is NE. The extraction rate of DA, NE and E from placenta is approximately 60%. The peripheral plasma levels of ACTH in pregnant women during labor are twice and 10 times as high as those observed in the corresponding umbilical arteries and in nonpregnant women respectively. At delivery they increase further. No significant differences are found between the values measured in the arterial cord blood and those in the venous cord blood and in the newborns. A way of explaining the prevalence of E and the higher ACTH/E ratio found in the mother in comparison with the fetus could be that in the mother the stress response to parturition is regulated mainly by the pituitary-adrenal axis, whereas in the fetus there is a prevalent stimulation of the sympathetic nervous system.

Adrenocorticotropic Hormone↗