Psychobiological evidence of the stress resilience fostering properties of a cosmetic routine.

Everyday life psychosocial stressors contribute to poor health and disease vulnerabilty. Means alternative to pharmacotherapy that are able to foster stress resilience are more and more under the magnifying glass of biomedical research. The aim of this study was to test stress resilience fostering properties of the self-administration of a cosmetic product enriched with essential oils. On day 0, fourty women, 25-50 years old, self-administered both the enriched cosmetic product (ECP) and a placebo one (PCP). Then, women were randomized for daily self-administration (from day 1 to 28) of either ECP (n = 20) or PCP (n = 20). On day 29, subjects underwent a psychosocial stress test (PST). Autonomic (heart rate and its variability) and neuroendocrine (salivary cortisol) parameters were assessed both on day 0 and 29. All subjects filled a number of psychological questionnaires in order to quantify anxiety, perceived stress, and mood profile, and were videorecorded during PST for non-verbal behavior evaluation. A single application of ECP produced an acute potentiation of cardiac parasympathetic modulation, which was not observed when placebo was used. Prolonged self-administration of ECP induced: (i) a dampening of the cortisol rise produced by PST, (ii) a reduction of state anxiety, (iii) a favorable change in mood profile, and (iv) a reduction of non-verbal behavior patterns that signal anxiety, motivational conflict and avoidance. In conclusion, this study suggests that the self-administration of a cosmetic cream enriched with essential oils should be considered as a stress resilience fostering strategy due to its favorable physiological, neuroendocrine and psychological effects.

Effect of anisotropy on ventricular vulnerability to unidirectional block and reentry by single premature stimulation during normal sinus rhythm in rat heart.

Single high-intensity premature stimuli when applied to the ventricles during ventricular drive of an ectopic site, as in Winfree's "pinwheel experiment," usually induce reentry arrhythmias in the normal heart, while single low-intensity stimuli barely do. Yet ventricular arrhythmia vulnerability during normal sinus rhythm remains largely unexplored. With a view to define the role of anisotropy on ventricular vulnerability to unidirectional conduction block and reentry, we revisited the pinwheel experiment with reduced constraints in the in situ rat heart. New features included single premature stimulation during normal sinus rhythm, stimulation and unipolar potential mapping from the same high-resolution epicardial electrode array, and progressive increase in stimulation strength and prematurity from diastolic threshold until arrhythmia induction. Measurements were performed with 1-ms cathodal stimuli at multiple test sites (n = 26) in seven rats. Stimulus-induced virtual electrode polarization during sinus beat recovery phase influenced premature ventricular responses. Specifically, gradual increase in stimulus strength and prematurity progressively induced make, break, and graded-response stimulation mechanisms. Hence unidirectional conduction block occurred as follows: 1) along fiber direction, on right and left ventricular free walls (n = 23), initiating figure-eight reentry (n = 17) and tachycardia (n = 12), and 2) across fiber direction, on lower interventricular septum (n = 3), initiating spiral wave reentry (n = 2) and tachycardia (n = 1). Critical time window (55.1 ± 4.7 ms, 68.2 ± 6.0 ms) and stimulus strength lower limit (4.9 ± 0.6 mA) defined vulnerability to reentry. A novel finding of this study was that ventricular tachycardia evolves and is maintained by episodes of scroll-like wave and focal activation couplets. We also found that single low-intensity premature stimuli can induce repetitive ventricular response (n = 13) characterized by focal activations.NEW & NOTEWORTHY We performed ventricular cathodal point stimulation during sinus rhythm by progressively increasing stimulus strength and prematurity. Virtual electrode polarization and recovery gradient progressively induced make, break, and graded-response stimulation mechanisms. Unidirectional conduction block occurred along or across fiber direction, initiating figure-eight or spiral wave reentry, respectively, and tachycardia sustained by scroll wave and focal activations.

Early maternal separation has mild effects on cardiac autonomic balance and heart structure in adult male rats.

Early life adverse experiences have long-term physiologic and behavioral effects and enhance stress sensitivity. This study examined the effects of maternal separation (MS) on cardiac stress responsivity and structure in adulthood. Male Wistar rats were separated from the dams for 3 h per day from postnatal days 2 through 15. When exposed to 5-day intermittent restraint stress (IRS) as adults, MS, and control rats showed similar acute modifications of cardiac sympathovagal balance, quantified via heart rate variability analysis. In addition, MS had no effect on cardiac pacemaker intrinsic activity (as revealed by autonomic blockade with scopolamine and atenolol) and did not affect the circadian rhythmicity of heart rate, neither before nor after IRS. However, MS differed from control rats in cardiac parasympathetic drive following IRS, which was heightened in the latter but remained unchanged in the former, both during the light and dark phases of the daily rhythm. The evaluation of adult cardiac structure indicated that stress experienced during a crucial developmental period induced only modest changes, involving cardiomyocyte hypertrophy, increased density of vascular structures, and myocardial fibrosis. The mildness of these functional-structural effects questions the validity of MS as a model for early stress-induced cardiac disease in humans.

Exercise training reduces PGE2 levels and induces recovery from steatosis in tumor-bearing rats.

The effects of endurance training on PGE (2) levels and upon the maximal activity of hepatic carnitine palmitoyltransferase (CPT) system were studied in rats bearing the Walker 256 carciosarcoma. Animals were randomly assigned to a sedentary control (SC), sedentary tumor-bearing (ST), exercised control (EC), and as an exercised tumor-bearing (ET) group. Trained rats ran on a treadmill (60% VO (2) max) for 60 min/day, 5 days/week, for 8 weeks. We examined the mRNA expression (RT-PCR) and maximal activity (radioassay) of the carnitine palmitoyltransferase system enzymes (CPT I and CPT II), as well as the gene expression of fatty-acid-binding protein (L-FABP) in the liver. PGE (2) content was measured in the serum, in tumor cells, and in the liver (ELISA). CPT I and CPT II maximal activity were decreased (p<0.01) in ST when compared with SC. In contrast, serum PGE (2) was increased (p<0.05) in cachectic animals as compared with SC. In the liver, PGE (2) content was also increased (p<0.05) when compared with SC. Endurance training restored maximal CPT I and CPT II activity in the tumor-bearing animals (p<0.0001). Exercise training induced PGE (2) levels to return to control values in the liver of tumor-bearing training rats (p<0.05) and decreased the eicosanoid content in the tumor (p<0.01). In conclusion, endurance training was capable of reestablishing liver carnitine palmitoyltransferase (CPT) system activity associated with decreased PGE (2) levels in cachectic tumor-bearing animals, preventing steatosis.

Synergistic acceleration of thyroid hormone degradation by phenobarbital and the PPAR alpha agonist WY14643 in rat hepatocytes.

Energy balance is maintained by controlling both energy intake and energy expenditure. Thyroid hormones play a crucial role in regulating energy expenditure. Their levels are adjusted by a tight feedback-controlled regulation of thyroid hormone production/incretion and by their hepatic metabolism. Thyroid hormone degradation has previously been shown to be enhanced by treatment with phenobarbital or other antiepileptic drugs due to a CAR-dependent induction of phase II enzymes of xenobiotic metabolism. We have recently shown, that PPAR alpha agonists synergize with phenobarbital to induce another prototypical CAR target gene, CYP2B1. Therefore, it was tested whether a PPAR alpha agonist could enhance the phenobarbital-dependent acceleration of thyroid hormone elimination. In primary cultures of rat hepatocytes the apparent half-life of T3 was reduced after induction with a combination of phenobarbital and the PPAR alpha agonist WY14643 to a larger extent than after induction with either compound alone. The synergistic reduction of the half-life could be attributed to a synergistic induction of CAR and the CAR target genes that code for enzymes and transporters involved in the hepatic elimination of T3, such as OATP1A1, OATP1A3, UGT1A3 and UGT1A10. The PPAR alpha-dependent CAR induction and the subsequent induction of T3-eliminating enzymes might be of physiological significance for the fasting-induced reduction in energy expenditure by fatty acids as natural PPAR alpha ligands. The synergism of the PPAR alpha agonist WY14643 and phenobarbital in inducing thyroid hormone breakdown might serve as a paradigm for the synergistic disruption of endocrine control by other combinations of xenobiotics.

p53 codon 72 polymorphism does not affect the risk of cervical cancer in patients from northern Italy.

A case-control study was performed to investigate the risk of cervical cancer associated with p53 polymorphism at codon 72, encoding either arginine or proline. It has been recently suggested that the arginine isoform increases the susceptibility to invasive cervical cancer; however, data remain controversial. The polymorphism was examined by both allele-specific PCR and RFLP analysis in 101 patients with primary cervical cancer and in 140 healthy women of the same age and from the same geographical area. The distribution of p53 genotypes in cervical cancer patients and in controls was not significantly different (P = 0.445), and homozygosity for arginine at residue 72 was not associated with an increased risk for cervical cancer (odds ratio, 0.81; 95% confidence interval, 0.47-1.42; P = 0.52). Similarly, different genotype distribution and increased risk were not observed when patients versus controls were analyzed according to human papillomavirus status and cancer histotype. Therefore, no evidence of association between homozygosity for p53 arginine and cervical cancer was found in our population sample.

Interferon-alpha in combination with ribavirin as initial treatment for hepatitis C virus-associated cryoglobulinemic membranoproliferative glomerulonephritis.

Mixed cryoglobulinemia (MC) and glomerulonephritis are the most important extrahepatic manifestations of chronic hepatitis C virus (HCV) infection. In HCV-infected patients with MC, renal involvement worsens the overall prognosis because of a high incidence of infection or cardiovascular disease. The relationship between MC and HCV infection has prompted the use of antiviral therapy. Two patients with chronic HCV infection, type-II MC and membranoproliferative glomerulonephritis (MPGN), presenting as nephrotic syndrome were treated with interferon (IFN)-alpha (3 MU 3 times per week) and ribavirin (15 mg/kg daily) for 6 months. Laboratory tests included measurement of anti-HCV antibodies, HCV RNA, and HCV genotyping, and characterization of circulating cryoglobulins. A pretreatment renal biopsy was performed, and the histopathologic lesions were scored according to the index of disease activity. Viremia and cryoglobulinemia were suppressed in both patients. However, a complete remission of proteinuria was observed in 1 patient only. The evaluation of the renal biopsy specimens revealed a mild MPGN (activity score: 5/24) in the patient with remission of proteinuria and a severe MPGN (activity score: 15/24) in the patient who maintained a nephrotic-range proteinuria. Although a fully satisfactory treatment is not yet available, we feel that a reasonable therapeutic strategy for HCV-infected patients with MC nephritis could be as follows: (1) antiviral treatment alone for patients with a low-grade kidney involvement, and (2) a short-term course of steroids and cytotoxic drugs followed by antiviral therapy for acute exacerbations and/or rapidly progressive GN.

Human papillomavirus types 16 and 18 infection in infiltrating adenocarcinoma of the cervix: PCR analysis of 138 cases and correlation with histologic type and grade.

The authors investigated by PCR 138 infiltrating cervical adenocarcinoma (27 grade 1, 76 grade 2, and 35 grade 3) for the presence of human papillomavirus (HPV) 16 and 18 infection. They included 95 (68.8%) mucinous and 43(31.2%) non-mucinous tumors. The overall prevalence of HPV infection was 84.8%; 28.3% of the cases were positive for HPV 16, 29.7% for HPV 18, and 26.8% for both HPVs. Amplification of HPV 16 and 18 negative cases with consensus primers MY09/MY11 failed to yield any additional tumors with HPV DNA sequences. Patients with HPV infection were younger than the patients who were HPV-negative (P = .001). The type of HPV was unrelated to age. Human papillomavirus infection was found in 95.8% mucinous and in 60.5% non-mucinous tumors (P < .001), with even distribution among grade 1, 2 and 3 adenocarcinoma. Our findings confirm the key role of HPV 16 and 18 in the development of cervical adenocarcinoma, particularly in mucinous histotypes. The absence of HPV infection, the old age of patients and the non-mucinous differentiation may identify a subset of cervical adenocarcinoma with different etiopathogenesis.

Primary retroperitoneal mucinous cystoadenocarcinomas: an immunohistochemical and molecular study.

Special immunohistochemical stains for the identification of gastroenteropancreatic antigens in two cases of primary retroperitoneal mucinous cystoadenocarcinomas (PRMC) show that these tumours have patterns similar to ovarian mucinous tumours. Markers of pyloric type gastric mucosa differentiation (M1, cathepsin E, concavavalin A, pepsinogen II) are mostly positive in benign and borderline areas with endocervical type differentiation, while immunoreactivity for intestinal cell markers (M3SI and CAR-5) and for DU-PAN-2 is present mainly in frankly malignant areas, regardless of differentiation type. DNA analysis shows a point mutation of K-ras oncogene at codon 12 (GGT to CGT) in one case. The immunohistochemical and genotypic similarity of PRMC and ovarian mucinous tumours may indicate similar mechanisms in their histogenesis.

Perinatal transmission of human papillomavirus from gravidas with latent infections.

OBJECTIVE: To evaluate the risk of perinatal human papillomavirus (HPV) transmission from mothers with latent infections to the oropharyngeal mucosae of their infants. METHODS: Seven hundred eleven mother-newborn pairs were tested. Polymerase chain reaction was done with MY09/MY11 consensus primers to identify HPV DNA in maternal cervicovaginal lavages and newborn nasopharyngeal aspirates. Positive cases were further amplified with type-specific primers for HPVs 6, 11, 16, 18, and 33. All infants born to HPV-positive mothers were observed to 18 months for appearance of HPV in oropharyngeal mucosae. RESULTS: Human papillomavirus DNA was detected in 11 neonates born vaginally to HPV-positive women, a vertical transmission rate was 30% (95% confidence interval [CI] 15.9, 47). Nasopharyngeal aspirates were HPV-negative in all 11 cases in which rupture of membranes occurred less than 2 hours before delivery. When rupture preceeded delivery by 2-4 hours, and when it occurred after more than 4 hours, the respective rates for HPV positivity were seven of 21 and four of five (chi2 for trend = 10.7, P = .001). At follow-up, virus was cleared from the oropharyngeal samples as early as the 5th week. CONCLUSION: Pregnant women with latent HPV infections have low potential of transmitting the virus to the oropharyngeal mucosae of their infants. The time between rupture of the amnion and delivery seems to be a critical factor in predicting transmission. Human papillomavirus-positive infants should be considered contaminated rather than infected since virus is cleared over several months after birth.

Haemangiopericytoma of the lacrimal sac: a case report.

A primary haemangiopericytoma of the lacrimal sac in a 45-year-old male is reported. The neoplasm, highly unusual in this location, recurred twice before being correctly identified. Total excision with surrounding tissue appears to be the treatment of choice for this tumour, the behaviour of which is often unpredictable.

Cervical adenocarcinomas express markers common to gastric, intestinal, and pancreatobiliary epithelial cells.

Frequency and pattern of expression of eight markers of gastric, intestinal, and pancreatobiliary duct epithelial cells have been investigated by histochemical and immunohistochemical techniques in 85 cases of cervical adenocarcinomas. M1, a mucin antigen, and Cathepsin E (CaE), an aspartic proteinase, markers of normal gastric superficial/foveolar epithelial cells, are expressed in 40 and 55 tumors, respectively. Periodic acid-concanavalin A-reactive mucin or Pepsinogen (PG) II, markers of gastric mucus neck and pyloric gland cells, are found in 24 tumors, 13 of which also express M1 and CaE. CAR-5 and M3SI, markers of intestinal mucin, are expressed in 68 and 12 tumors and DU-PAN-2, marker of normal pancreatobiliary duct cells, is found in 46 tumors. All but two tumors express at least one of the eight markers studied, none express PG I, marker of gastric chief cells. The different histologic subtypes of cervical adenocarcinomas expressed to a variable degree both gastrointestinal and pancreatobiliary markers. Only endocervical type tumors, however, showed the full spectrum of mucosal pyloric type differentiation, including the expression of PGII which is not present in any other histotype. A correlation between expression of gastroenteropancreatic markers and tumor grade is not apparent in our series.

Granular cell traumatic neuroma: a lesion occurring in mastectomy scars.

BACKGROUND: Granular cell changes can be observed in a variety of benign and malignant tumors, and are seen more commonly in granular cell tumors, which in about 5% of cases develop in the breast. Granular cells also have been observed in sites of previous trauma, such as surgery, and are found to be inflammatory reactions of histiocytic origin. METHODS AND RESULTS: We investigated, morphologically and immunohistochemically, 2 granular cell lesions occurring in mastectomy scars after surgery for carcinoma. Both lesions were composed of strands and nests of large granular cells, haphazardly set in a background of fibrous tissue, with sparse inflammatory infiltrates. Several tortuous hypertrophic nerve bundles were also embedded in the fibrous tissue. A few of these nerve bundles showed degenerative changes and contained granular cells. Immunohistochemically, granular cells were positive for S100 protein, neuron-specific enolase, vimentin, and CD68 antigen. CONCLUSIONS: We consider these proliferative lesions of peripheral nerves to have the features of both granular cell tumor and traumatic neuroma. These cases indicate that traumatic neuroma can undergo extensive granular cell changes and constitute a previously unrecognized entity, which we provisionally label granular cell traumatic neuroma. Granular cell traumatic neuroma has to be taken into consideration when evaluating lesions occurring at mastectomy scars and should be differentiated from malignant tumors with granular cells, such as apocrine carcinoma and alveolar soft part sarcoma.

Fluorescent in situ hybridisation on tissue sections: a quantitative approach with confocal laser scanning microscopy.

The use of fluorescent detection methods in association with digital microscopy technologies is an innovative approach for tissue localisation of messenger RNA. The success of such methods relies on the tissue preservation, local availability of the probe and on the existence of high resolution tridimensional analysis systems. Cryostatic sections, mild denaturation, short oligonucleotide probes (20mer) and confocal laser scanning microscopy allow the fulfillment of all these conditions avoiding photobleaching and tissue autofluorescence. In this paper, we describe in detail a method for in situ hybridisation set up with digoxigenin-coupled oligonucleotide complementary to beta-actin mRNA as a probe and an anti-hapten fluorescent antibody as second step for detecting specific hybridisation. Fluorescence was analysed by means of a confocal laser scanning microscope (CLSM) that provides images with low out-of-focus blurring also with relatively low numerical aperture (NA) objectives. We propose also an easy method to perform semi-quantitative thresholding analysis which allows to discriminate between background and specific signal.

Sclerosing stromal tumour of the ovary. Ultrastructural study.

Two typical cases of sclerosing stromal tumours of the ovary are studied ultrastructurally, and the findings are correlated with the clinical data. One of the cases, with predominantly fibroblastic morphology, was asymptomatic. The second case, rich in cells with steroid-secreting features, had polymenorrhoea disappearing after removal of the tumour. The Authors suggest that clinical symptoms of sclerosing stromal tumour of the ovary depend from the degree of differentiation reached by the tumour cells.

Dedifferentiating endometrial adenocarcinoma. Report of a case.

A case of well differentiated endometrial adenocarcinoma in a 70 year-old patient is reported, which evolved to undifferentiated small cell after being treated with chemotherapy for six months. The possible mechanisms of dedifferentiation are briefly discussed.

Cytology of malignant mixed mesodermal tumour of the uterus: experience of 10 cases.

The value of cytology as a diagnostic tool in uterine MMMT has been tested in order to reach an earlier diagnosis. From 10 endocervical scrapings we were able to obtain 7 positive smears, two of them diagnostic for mixed tumour at first examination, 1 detected upon revision. In one case the positive smear was obtained from a direct scraping of the neoplasia protruding through the cervical os.

[Asymptomatic Chagas disease. Electrocardiographic and echocardiographic findings]. / Chagas asintomático. Hallazgos electrocardiográficos y ecocardiográficos.

A total of 70 blood-donor volunteers were studied to determine the utility of the echocardiogram and Doppler in the diagnosis of cardiopathies in asymptomatic patients with Chagas disease. These patients came from endemic areas and had humoral positive reactions for South American Trypanosomiasis. They were checked against a control group of blood-donors with no environmental antecedents and with negative reactions. Both groups were similar in age and sex. The chagasic group showed an abnormal electrocardiogram in twelve cases (17.4%), being left anterior hemiblock the most frequent alteration found (nine cases, 62.5%). In the control group no alterations were found (p = 0.0005). The echocardiogram and Doppler were abnormal in 29 cases of the chagasic group (38.8%): alterations in ventricular relaxation were found in 8 cases (27.6%), enlargement of cavities in 9 (31%), both phenomena in 9 (31%) and alteration of parietal motility in 3 (10.3%). In the control group, 1 case presented alteration in ventricular relaxation (p = 0.000008). These results confirmed that the abnormal discoveries were related to Chagas disease. Out of 70 chagasic patients, 31 (44.29%) showed some alteration in the tests: 12 had an abnormal electrocardiogram, and of these only 2 had normal echocardiogram and Doppler, the rest showed abnormal echocardiogram and Doppler. Other 29 (of these 70 patients) showed some alteration in the echocardiogram and Doppler, and 20 of them presented a normal electrocardiogram. It can be concluded that the echocardiogram and Doppler are more accurate to detect cardiac involvement in asymptomatic chagasic patients than the electrocardiogram, showing abnormality in many cases where there are no electrocardiographic alterations. On the other hand, patients with abnormal electrocardiogram and Doppler are less frequent. Therefore, to define the undetermined period of Chagas disease echocardiogram and Doppler should be incorporated as a routine resource of diagnosis considering the high percentage of cases in which cardiac participation is detected when there is no clinic, radiologic and electrocardiographic disturbance.

Effect of exhaustive ultra-endurance exercise in muscular glycogen and both Alpha1 and Alpha2 Ampk protein expression in trained rats.

Glycogen is the main store of readily energy in skeletal muscle and plays a key role in muscle function, demonstrated by the inability to sustain prolonged high-intensity exercise upon depletion of these glycogen stores. With prolonged exercise, glycogen depletion occurs and 5'-AMP-activated protein kinase (AMPK), a potent regulator of muscle metabolism and gene expression, is activated promoting molecular signalling that increases glucose uptake by muscular skeletal cells. The aim of this study was primarily to determine the effect of ultra-endurance exercise on muscle glycogen reserves and secondly to verify the influence of this type of exercise on AMPK protein expression. Twenty-four male Wistar rats, 60 days old, were divided into four experimental groups: sedentary, sedentary exhausted (SE), endurance trained (T) and endurance trained exhausted (TE). The animals ran for 10 to 90 min/day, 5 days/week, for 12 weeks to attain trained status. Rats were killed immediately after the exhaustion protocol, which consisted of running on a treadmill (at approximately 60% Vmax until exhaustion). Optical density of periodic acid-Schiff was detected and glycogen depletion observed predominantly in type I muscle fibres of the TE group and in both type I and II muscle fibres in the SE group. Plasma glucose decreased only in the TE group. Hepatic glycogen was increased in T group and significantly depleted in TE group. AMPK protein expression was significantly elevated in TE and T groups. In conclusion, acute exhaustive ultra-endurance exercise promoted muscle glycogen depletion. It seems that total AMPK protein and gene expression is more influenced by status training.

Social defeat and isolation induce clear signs of a depression-like state, but modest cardiac alterations in wild-type rats.

Adverse social environments play a relevant role in the onset and progression of mood disorders. On the other hand, depression is an independent risk factor for cardiovascular morbidity. This study was aimed at (i) corroborating the validity of a rat model of depression based on a negative social episode followed by social isolation and (ii) verifying its impact on cardiac function and structure. Pair housed, wild-type Groningen rats (Rattus norvegicus) were implanted with radiotransmitters for ECG, temperature and activity recordings. They were either exposed to a social defeat episode followed by 4-week isolation or left undisturbed with their female partners. The social challenge induced a series of biological changes that are commonly taken as markers of depression in rats, including decreased body weight gain and reduced preference for sucrose consumption, functional and structural changes of the hypothalamic-pituitary-adrenocortical axis, increased anxiety in the elevated plus maze test. The cardiovascular alterations consisted in (i) transitory heart rate circadian rhythm alterations, (ii) lack of habituation of cardiac autonomic responsivity (tachycardia and vagal withdrawal) to an acute stressor, and (iii) moderate hypertrophy affecting the right ventricle of the heart. These results indicate that a depression-like state induced via this model of social challenge was associated with a few modest cardiovascular changes. Further studies are required to confirm the validity of this rat model of depression as a valid preclinical approach to the comprehension of the biological substrates underlying depression-cardiovascular comorbidity.