Odontogenic tumours in a Chilean population: a retrospective study of 544 cases based on 2022 WHO classification.

BACKGROUND: Odontogenic tumours are infrequent lesions. Studies on the frequency of odontogenic tumours from Latin America are scarce. This work aimed to determine the relative frequency of odontogenic tumours in a Chilean population using the 2022 World Health Organization classification. MATERIAL AND METHODS: This is a case series retrospective study. We reviewed 35,530 samples from 1975 to 2022 from the Oral Pathology Referral Institute and the Pathological Anatomy Service, Faculty of Dentistry, University of Chile. We utilized the 2022 World Health Organization classification for histological typification. RESULTS: According to 2022 World Health Organization classification, 544 odontogenic tumours were confirmed. The most frequent odontogenic tumours were: odontoma (n=241; 44.3%), ameloblastoma (n=109; 20.0%) and cemento-ossifying fibroma (n=71; 13.1%). Benign odontogenic tumours corresponded to 538 cases (98.9%) and malignant tumours were only six cases (1.1%). CONCLUSIONS: In our population, odontoma was the most frequent odontogenic tumour followed by ameloblastoma and cemento-ossifying fibroma. Malignant odontogenic tumours were very rare. The results of this study are similar to reports from America, but there are some differences concerning the data from Africa and Asia.

Tofacitinib in patients with moderate-to-severe chronic plaque psoriasis: long-term safety and efficacy in an open-label extension study.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor. Final safety and efficacy data from an open-label extension study of tofacitinib in psoriasis are reported. OBJECTIVES: To evaluate the long-term safety and durability of efficacy of tofacitinib in adults with moderate-to-severe chronic plaque psoriasis. METHODS: Eligible patients who completed qualifying phase II/III tofacitinib studies received tofacitinib 10 mg twice daily (q12h) until month 3; subsequently, the dose could be adjusted by investigators to either 5 or 10 mg q12h. Adverse events (AEs) are reported up to month 66 and laboratory data up to month 54. Efficacy end points up to month 54 included Physician's Global Assessment of 'clear' or 'almost clear' (PGA response) and 75% improvement in Psoriasis Area and Severity Index (PASI 75). RESULTS: Overall, 2867 patients received tofacitinib, with a median treatment duration of 35·6 months. Adverse events (AEs) and serious AEs were reported in 82·5% and 13·7% of patients, respectively; 13·9% of patients discontinued owing to AEs; and 29 patients died. Incidence rates (patients with event/100 patient-years) were 1·16 for serious infections, 0·67 for malignancies and 0·26 for major adverse cardiovascular events. After initial changes in qualifying studies, most laboratory parameters were generally stable over 54 months. PGA response was achieved by 52-62% of patients and PASI 75 by 56-74% of patients at each study visit through month 54. CONCLUSIONS: In patients with psoriasis, the safety profile of tofacitinib over 66 months was similar to previous reports in phase III studies and efficacy was sustained through 54 months (NCT01163253).

Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis: Subgroup analysis of Latin American patients in the phase 3 randomized UNCOVER-3 study.

BACKGROUND AND OBJECTIVES: Ixekizumab demonstrated greater efficacy than placebo and etanercept in UNCOVER-3. Subgroup analysis of Latin American patients was performed. We report 12-week and 60-week data. PATIENTS AND METHODS: Analysis included 102 Latin American patients randomized to receive placebo (n=14), etanercept 50mg twice weekly (n=30), or ixekizumab 160-mg starting dose followed by 80mg every 2 weeks (Q2W; n=29) or every 4 weeks (Q4W; n=29). At week 12, patients maintaining efficacy response and adequate overall safety were assigned, at the discretion of the investigator, to long-term extension with ixekizumab Q4W. RESULTS: At week 12, Psoriasis Area and Severity Index (PASI) 100 scores were 0%, 20.0% (p=0.075 vs placebo), 62.1% (p<0.001 vs placebo; p=0.001 vs etanercept), and 48.3% (p=0.002 vs placebo; p=0.023 vs etanercept) for placebo, etanercept, ixekizumab Q2W, and ixekizumab Q4W, respectively. Among patients who continued therapy up to week 60 (n=97), PASI 100 scores were 71.4%, 60.0%, 77.8%, and 57.7% for patients who received induction placebo, etanercept, ixekizumab Q2W, and ixekizumab Q4W, respectively (non-responder imputation). By week 60, ≥1 serious adverse event was experienced by 7.1% (n=1/14), 3.3% (n=1/30), 14.8% (n=4/27), and 0% (n=0/26) of patients who received induction placebo, etanercept, ixekizumab Q2W, and ixekizumab Q4W, respectively. There were no cases of active tuberculosis with ixekizumab treatment through 60 weeks. CONCLUSIONS: In Latin American patients, both ixekizumab dosing regimens demonstrated greater efficacy than etanercept for treating psoriasis over 12 weeks. The safety profile of ixekizumab through 60 weeks was well tolerated and consistent with the overall profile.

Is the snail shell repair process really influenced by eggshell membrane as a template of foreign scaffold?

Biominerals are inorganic-organic hybrid composites formed via self-assembled bottom up processes under mild conditions. Biominerals show interesting physical properties, controlled hierarchical structures and robust remodeling or repair mechanisms. Biological processes associated with biominerals remain to be developed into practical engineering processes. Therefore, the formation of biominerals is inspiring for the design of materials, especially those fabricated at ambient temperatures. The study described herein involves the influence of chicken outer eggshell membrane on the type of calcium carbonate (CaCO3) polymorph deposited on the shell of the land snail Helix aspersa during the repair process after an injury. A piece of snail shell was removed by perforating a hole from the largest body whorl. The operated area was left either uncovered or covered with either a thermoplastic flexible polyolefin-based film Parafilm® or a piece of chicken eggshell membrane. The repaired shells of control and experimental animals were analyzed using SEM, EDS, Raman and FTIR spectroscopies. We found that in the presence of eggshell membrane, the polymorph deposited on the substratum during the first hours resembles calcite, the polymorph present in eggshell normal formation, but at 24 and 48h, when snail mantle cells produced their normal organic matrix (mainly ß-chitin plus proteins and proteoglycans), the polymorph deposited is aragonite, the characteristic polymorph of Helix shell. Therefore, the eggshell membrane influences the type of polymorph, but only in the initial stages of biomineral deposition, before an organic matrix layer is deposited by the snail.

Tofacitinib versus etanercept or placebo in patients with moderate to severe chronic plaque psoriasis: patient-reported outcomes from a Phase 3 study.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor that is being investigated for psoriasis. Psoriasis impacts on physical and psychological well-being; improvements in health-related quality of life (HRQoL) with etanercept in psoriasis are well documented. OBJECTIVE: To evaluate HRQoL with tofacitinib, vs. placebo or etanercept, in the Phase 3, randomized, placebo-controlled, non-inferiority, Oral-treatment Psoriasis Trial (OPT) Compare Study (NCT01241591). METHODS: Adults with moderate to severe chronic plaque psoriasis were randomized 3:3:3:1 to tofacitinib 10 or 5 mg twice daily (BID), etanercept 50 mg twice weekly or placebo, for 12 weeks. Patient-reported outcomes (PROs) included Dermatology Life Quality Index (DLQI), Itch Severity Item and Patient Global Assessment of psoriasis. RESULTS: At baseline, 83.4% (911/1092) of patients had a DLQI score ranging between 6 and 30, indicating a substantial burden of disease. By Week 12, 47.3%, 43.6% and 30.9% of patients in the tofacitinib 10 mg BID, etanercept and tofacitinib 5 mg BID groups, respectively, had a DLQI score of 0 or 1 (no effect of psoriasis on QoL) vs. 7.8% for placebo (all P < 0.0001). Tofacitinib significantly reduced itch vs. placebo (P < 0.05 both doses) and etanercept (P < 0.0001 both doses) within 1 day of starting treatment. Furthermore, reductions in itch were greater with tofacitinib 10 mg BID, vs. etanercept, at Weeks 2-12 (all time points P < 0.05). At Week 2, an Itch Severity Item score of 'little or no itch' was more frequent with tofacitinib 10 mg (68.6%) vs. etanercept (57.4%) and placebo (12.2%), and the PtGA response rate was significantly greater with tofacitinib 10 mg vs. placebo (P < 0.05). CONCLUSION: Oral tofacitinib provided significant improvements across multiple PROs by Week 12. Improvements with tofacitinib 10 mg BID were comparable to etanercept, and improvements in itch were greater and more rapid with tofacitinib 10 mg BID.

Prediction of rectal temperature using non-invasive physiologic variable measurements in hair pregnant ewes subjected to natural conditions of heat stress.

Rectal temperature (RT) is the foremost physiological variable indicating if an animal is suffering hyperthermia. However, this variable is traditionally measured by invasive methods, which may compromise animal welfare. Models to predict RT have been developed for growing pigs and lactating dairy cows, but not for pregnant heat-stressed ewes. Our aim was to develop a prediction equation for RT using non-invasive physiological variables in pregnant ewes under heat stress. A total of 192 records of respiratory frequency (RF) and hair coat temperature in various body regions (i.e., head, rump, flank, shoulder, and belly) obtained from 24 Katahdin × Pelibuey pregnant multiparous ewes were collected during the last third of gestation (i.e., d 100 to lambing) with a 15 d sampling interval. Hair coat temperatures were taken using infrared thermal imaging technology. Initially, a Pearson correlation analysis examined the relationship among variables, and then multiple linear regression analysis was used to develop the prediction equations. All predictor variables were positively correlated (P<0.01; r=0.59-0.67) with RT. The adjusted equation which best predicted RT (P<0.01; Radj(2)=56.15%; CV=0.65%) included as predictors RF and head and belly temperatures. Comparison of predicted and observed values for RT indicates a suitable agreement (P<0.01) between them with moderate accuracy (Radj(2)=56.15%) when RT was calculated with the adjusted equation. In general, the final equation does not violate any assumption of multiple regression analysis. The RT in heat-stressed pregnant ewes can be predicted with an adequate accuracy using non-invasive physiologic variables, and the final equation was: RT=35.57+0.004 (RF)+0.067 (heat temperature)+0.028 (belly temperature).

Thermoregulation of nutrient-restricted hair ewes subjected to heat stress during late pregnancy.

In summers with severe hot environmental temperatures, thermoregulation is expected to be critical during the last third of gestation of hair ewes, and this effect can be overstated by suboptimal feeding conditions. Twenty-four multiparous hair sheep ewes with approximately 100d of pregnancy were randomly assigned to two treatments to evaluate the effects of nutritional restriction (NR) during late gestation on some serum metabolites, physiological variables, and thyroid hormone concentrations under intense heat load (maximum temperature 42-45°C). Treatments were as follows: (1) control, ewes fed free choice wheat straw plus a concentrate at a rate of 500g/d, and (2) nutritionally-restricted (NR) ewes, which were offered wheat straw only ad libitum. Body weight of NR ewes dropped 5.1kg (P<0.05), while control ewes gained 4.7kg during the study period. Rectal temperature was not affected (P>0.05) by feeding regime either in the morning or afternoon hours. Respiration rate was greater (P<0.05) in control ewes (20 and 40breaths/min higher in the day and night, respectively) on d 130 and 145 of pregnancy compared to NR ewes. Skin temperatures during the morning and afternoon were affected (P<0.05) by feeding regime at d 130 and 145 of pregnancy. In the morning, NR ewes presented greater (P<0.05) head and rump temperature at day 145 of gestation, and lower (P<0.05) udder temperatures at d 130 and 145 than control ewes. In the afternoon, skin temperatures of NR ewes were higher (P<0.05) in head and right flank on d 130 and 145 of pregnancy, and in udder at day 145 compared to control ewes. Serum glucose was higher (P<0.05) in NR ewes than control animals at day 145 of pregnancy. Serum cholesterol, triglyceride and thyroid hormones were not affected by nutritional restriction. Overall, it was found that nutritionally restricted ewes were less affected by intense heat loads than well-fed ewes, apparently due to the lower metabolic heat produced by this underfed animals. Also, it was apparent that the lower respiration rate of NR ewes was compensated by a greater body surface temperature.

Physiological and productive responses of multiparous lactating Holstein cows exposed to short-term cooling during severe summer conditions in an arid region of Mexico.

Heat stress generates a significant economic impact for the dairy industry in arid and semi-arid regions of the world, so that heat abatement is an important issue for dairy producers. The objective of this study was to evaluate effects of two short-term cooling periods on physiological and productive status of lactating Holstein cows during hot ambient temperatures. Thirty-nine multiparous cows were blocked by milk yield and assigned to one of three treatments including: control group (C), cows cooled before milking time (0500 and 1700 h daily, 1 h cooling); AM group, cows cooled at 1000 h and before milking (2 h cooling); and AM + PM group, cows cooled at 1100, 1500 and 2200 h, as well as before milking (4 h cooling). The cooling system was placed in the holding pen which the cows were moved through for cooling. Respiratory rate, and temperatures of thurl and right flank, were lower (P < 0.05) in cows from the AM + PM group than AM and C cows during the morning and afternoon. However, udder temperature was higher in the AM + PM group compared to AM and C groups during the afternoon, although lower than the AM group during the morning. Rectal temperature was similar in all groups. Thyroxin concentrations tended (P < 0.10) to be lower in AM + PM relative to the AM and C groups. The AM + PM group had higher (P < 0.05) milk production than C (18.70 vs. 17.43 kg, respectively), and AM + PM cows had a trend (P < 0.10) to increased milk energy output vs. the C and AM groups (13.75 vs. 13.18 and 13.15 Mcal, respectively). Protein and fat in milk, body condition score, glucose, cholesterol, triglycerides and triiodothyronine were similar among the groups. Four hours of cooling with spray and fans during severe summer temperatures only modestly improved milk yield of lactating Holstein cows.

Melatonin exerts direct inhibitory actions on ACTH responses in the human adrenal gland.

In nonhuman primates and rodents, melatonin acting directly on the adrenal gland, inhibits glucocorticoid response to ACTH. In these species, an intrinsic adrenal circadian clock is involved in ACTH-stimulated glucocorticoid production. We investigated whether these findings apply to the human adrenal gland by determining i) expression of clock genes in vivo and ii) direct effects of melatonin in ACTH-stimulated adrenal explants over a) expression of the clock genes PER1 (Period 1) mRNA and BMAL1 [Brain-Muscle (ARNT)-like] protein, ACTH-induced steroidogenic acute regulatory protein (StAR), and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) and b) over cortisol and progesterone production. Adrenal tissue was obtained from 6 renal cancer patients undergoing unilateral nephrectomy-adrenalectomy. Expression of the clock genes PER1, PER2, CRY2 (Cryptochrome 2), CLOCK (Circadian Locomotor Output Cycles Kaput) and BMAL1, was investigated by RT-PCR in a normal adrenal and in an adenoma. In independent experiments, explants from 4 normal adrenals were preincubated in culture medium (6 h) followed by 12 h in: medium alone; ACTH (100 nM); ACTH plus melatonin (100 nM); and melatonin alone. The explants' content of PER1 mRNA (real-time PCR) and StAR, 3ß-HSD, BMAL1 (immuno slot-blot), and their cortisol and progesterone production (RIA) were measured. The human adrenal gland expresses the clock genes PER1, PER2, CRY2, CLOCK, and BMAL1. ACTH increased PER1 mRNA, BMAL1, StAR, and 3ß-HSD protein levels, and cortisol and progesterone production. Melatonin inhibited these ACTH effects. Our study demonstrates, for the first time, direct inhibitory effects of melatonin upon several ACTH responses in the human adrenal gland.

Epidemiology and quality of life of patients with psoriasis in Chile.

BACKGROUND: Clinical characteristics of psoriasis vary between different races and climates. There are few data on Latin American and even fewer on Chilean patients with psoriasis. OBJECTIVES: To assess that clinical characteristics and quality of life (QoL) of a group of Chilean patients with psoriasis. METHODS: A cross-sectional, observational and analytic study was conducted at the Dermatology Department of the Clinical Hospital of the University of Chile between July 2006 and December 2008 applying an epidemiological and QoL-related survey to psoriatic patients. RESULTS: One hundred fifty-three patients with psoriasis were included in the study. The mean (SD) age was 42.7 (14.9) years and 60.1% of the patients were male. The most frequent disease subtype was plaque psoriasis (71.9%), followed by "guttatiform" (guttate morphology without confirmed streptococcal infection) psoriasis (17.7%). In 38.6% of patients, less than 10% of body surface area (BSA) was affected. Joint involvement was reported in 28.8% of patients. Those with early onset of disease (before 30 years of age) were more likely to have a positive family history of psoriasis. Hypertension and diabetes were present in 20.3% and 11.1% of patients, respectively. The mean Dermatology Life Quality Index was 14. Greater impact of the disease on QoL was associated with male sex, young age of onset, newly diagnosed disease, facial involvement, and widespread disease. CONCLUSION: Chilean patients with psoriasis have clinical characteristics and QoL comparable to patients in other countries. A notable difference, however, was the greater impact of psoriasis on the QoL of Chilean men compared to women.

Ovarian thecoma: A very unusual cause of postmenopausal bleeding.

We describe a 67-year-old woman with postmenopausal bleeding having ceased estrogen plus progestogen therapy nine months before. Transvaginal ultrasonography showed endometrial thickening with normal ovarian appearance. Hormonal studies revealed high estradiol and inhibin B levels but normal androgens and adrenal hormones. Magnetic resonance image demonstrated a 13-mm left ovarian tumour. Hysterectomy and bilateral salpingo-oophorectomy were performed, and the pathological study revealed an 8 mm ovarian thecoma. This case illustrates a very unusual cause of postmenopausal bleeding. We suggest a study protocol and discuss the differential diagnosis of this case.

Effect of Cervical Lesions on Fracture Resistance and Failure Mode of Maxillary Central Incisors Restored with Fiber Posts and Complete Crowns.

PURPOSE: To investigate the effect of a cervical cavity extending 1 mm apical to the cemento-enamel junction (CEJ) on fracture resistance and failure mode of maxillary central incisors that have been treated endodontically, present with complete and incomplete ferrules, and are restored with and without a fiber post. METHODS AND MATERIALS: 50 intact human maxillary central incisors were divided into five groups (n=10): CG (control group) 6-mm fer-rule height, no cervical cavity, and without post; (CO) 6-mm ferrule height without post, with a cervical cavity (access to root canal and cervical cavity restored with composite resin), cervical cavity; and post with ferrule heights of 1 mm (CP1), 2 mm (CP2), and 6 mm (CP6) restored with fiberglass post and composite resin core. After complete metal crowns were cemented on all specimens, they were subjected to thermal cycling (6000 cycles, 5°C/55°C), followed by immediate testing of fracture resistance. After failure, the specimens were sectioned buccolingually to evaluate and identify the mode of failure. The data were analyzed with an analysis of variance (ANOVA) and the Student-Newman-Keuls multiple comparison tests (α =0.05). RESULTS: A 1-mm ferrule height (CP1) fracture resistance was significantly lower (531±125 N) compared to the 6-mm ferrule height (CP6) (769±175 N) (p<0.05). With respect to the groups with similar residual dentin, with and without a cervical cavity, CG (667±119 N) and CO (668±119 N), the presence of a post (CP6) increased the resistance to fracture, although no statistically significant difference was demonstrated. Partial decementation was observed in all specimens of CG and CP6, in nine of CP1 and CP2, and in three in CO. Root fractures occurred in 23 specimens. The root surface was exposed 2 mm below the CEJ to simulate bone level. Propagation of subosseous cracks occurred in four specimens in CG and CP2, in seven specimens in CP6, in two specimens in CP1, and in six specimens in CO. All were considered catastrophic failures. CONCLUSIONS: Within the limitations of this study it is suggested that, when restoring an endodontically treated maxillary central incisor that has a cervical lesion and needs to be restored with a complete crown, a fiber post is cemented to improve fracture resistance.

Involvement of the transcription factor STAT1 in the regulation of porcine ovarian granulosa cell functions treated and not treated with ghrelin.

The aim of our in vitro experiments was to study the role of the transcription factor STAT1 and the hormone ghrelin in controlling porcine ovarian function. The effects of treatment with ghrelin (0, 1, 10, 100 ng/ml), transfection-induced overexpression of transcription factor STAT1, and their combination on apoptosis (expression of apoptosis-related peptides caspase-3, BAX and anti-apoptotic peptide BCL2), proliferation (expression of proliferating cell nuclear antigene PCNA, proliferation-associated protein kinase MAPK/ERK1,2) and release of the hormones progesterone (P(4)), prostaglandin F (PGF) and oxytocin (OXT) in cultured porcine ovarian granulosa cells was evaluated using RIA, immunocytochemistry and SDS-PAGE-western immunoblotting. It was found that ghrelin, when given alone, increased the expression of proliferation-associated PCNA and MAPK/ERK1,2, decreased the accumulation of apoptosis-related substances caspase-3, BAX, BCL2, decreased P(4), and increased PGF and OXT release. Ghrelin tended to promote accumulation of STAT1 in both control and transfected cells, although in transfected cells ghrelin at 1 ng/ml decreased STAT1 accumulation. Transfection of porcine granulosa cells by a gene construct encoding STAT1 promoted the expression of STAT1 and apoptosis-related-BAX but the expression of BCL2 did not, and decreased the accumulation of proliferation-associated MAPK/ERK1,2 but not that of PCNA. It also promoted PGF and OXT but not P(4) release. Overexpression of STAT1 reversed the effect of ghrelin on STAT1, PCNA, PGF, OXT (from stimulatory to inhibitory), BCL2, P(4) (from inhibitory to stimulatory), prevented ghrelin effect on caspase-3 and BAX, but did not affect ghrelin's effect on MAPK/ERK1,2 expression. These results suggest that ghrelin directly affects porcine ovarian cells function - stimulates proliferation, inhibits apoptosis and affects secretory activity. Furthermore, they demonstrated the involvement of the transcription factor STAT1 in controlling these functions, the promotion of some markers of apoptosis (BAX), inhibition of some markers of proliferation (MAPK/ERK1,2) and stimulation of PGF release. Finally, the obtained data failed to demonstrate that STAT1 is involved in mediating the action of ghrelin on ovarian cell functions.

Dry eye is matched by increased intrasubject variability in tear osmolarity as confirmed by machine learning approach. / El ojo seco está relacionado con un aumento intrasujeto de la variabilidad de osmolaridad lagrimal confirmado por tecnología de aprendizaje de máquinas.

OBJECTIVE: Because of high variability, tear film osmolarity measures have been questioned in dry eye assessment. Understanding the origin of such variability would aid data interpretation. This study aims to evaluate osmolarity variability in a clinical setting. MATERIAL AND METHODS: Twenty dry eyes and 20 control patients were evaluated. Three consecutive osmolarity measurements per eye at 5min intervals were obtained. Variability was represented by the difference between both extreme readings per eye. Machine learning techniques were used to quantify discrimination capacity of tear osmolarity for dry eye. RESULTS: Mean osmolarities in the control and dry eye groups were 295.1±7.3mOsm/L and 300.6±11.2mOsm/L, respectively (P=.004). Osmolarity variabilities were 7.5±3.6mOsm/L and 16.7±11.9mOsm/L, for the control and dry eye groups, respectively (P<.001). Based on osmolarity, a logistic classifier showed an 85% classification accuracy. CONCLUSIONS: In the clinical setting, both mean osmolarity and osmolarity variability in the dry eye group were significantly higher than in the control group. Machine learning techniques showed good classification accuracy. It is concluded that higher variability of tear osmolarity is a dry eye feature.

Clock gene expression in adult primate suprachiasmatic nuclei and adrenal: is the adrenal a peripheral clock responsive to melatonin?

The circadian production of glucocorticoids involves the concerted action of several factors that eventually allow an adequate adaptation to the environment. Circadian rhythms are controlled by the circadian timing system that comprises peripheral oscillators and a central rhythm generator located in the suprachiasmatic nucleus (SCN) of the hypothalamus, driven by the self-regulatory interaction of a set of proteins encoded by genes named clock genes. Here we describe the phase relationship between the SCN and adrenal gland for the expression of selected core clock transcripts (Per-2, Bmal-1) in the adult capuchin monkey, a New World, diurnal nonhuman primate. In the SCN we found a higher expression of Bmal-1 during the h of darkness (2000-0200 h) and Per-2 during daytime h (1400 h). The adrenal gland expressed clock genes in oscillatory fashion, with higher values for Bmal-1 during the day (1400-2000 h), whereas Per-2 was higher at nighttime (about 0200 h), resulting in a 9- to 12-h antiphase pattern. In the adrenal gland, the oscillation of clock genes was accompanied by rhythmic expression of a functional output, the steroidogenic enzyme 3beta-hydroxysteroid dehydrogenase. Furthermore, we show that adrenal explants maintained oscillatory expression of Per-2 and Bmal-1 for at least 36 h in culture. The acrophase of both transcripts, but not its overall expression along the incubation, was blunted by 100 nm melatonin. Altogether, these results demonstrate oscillation of clock genes in the SCN and adrenal gland of a diurnal primate and support an oscillation of clock genes in the adrenal gland that may be modulated by the neurohormone melatonin.

Transcription factor p53 can regulate proliferation, apoptosis and secretory activity of luteinizing porcine ovarian granulosa cell cultured with and without ghrelin and FSH.

The aim of our in vitro experiments was to examine the role of transcription factor p53 in controlling the basic functions of ovarian cells and their response to hormonal treatments. Porcine ovarian granulosa cells, transfected and non-transfected with a gene construct encoding p53, were cultured with ghrelin and FSH (all at concentrations of 0, 1, 10, or 100 ng/ml). Accumulation of p53, of apoptosis-related (MAP3K5) and proliferation-related (cyclin B1) substances was evaluated by immunocytochemistry. The secretion of progesterone (P(4)), oxytocin (OT), prostaglandin F (PGF), and E (PGE) was measured by RIA. Transfection with the p53 gene construct promoted accumulation of this transcription factor within cells. It also stimulated the expression of a marker of apoptosis (MAP3K5). Over-expression of p53 resulted in reduced accumulation of a marker of proliferation (cyclin B1), P(4), and PGF secretion and increased OT and PGE secretion. Ghrelin, when added alone, did not affect p53 or P(4), but reduced MAP3K5 and increased PGF and PGE secretion. Over-expression of p53 reversed the effect of ghrelin on OT, caused it to be inhibitory to P(4) secretion, but did not modify its action on MAP3K5, PGF, or PGE. FSH promoted the accumulation of p53, MAP3K5, and cyclin B1; these effects were unaffected by p53 transfection. These multiple effects of the p53 gene construct on luteinizing granulosa cells, cultured with and without hormones 1) demonstrate the effects of ghrelin and FSH on porcine ovarian cell apoptosis and secretory activity, 2) confirm the involvement of p53 in promoting apoptosis and inhibiting P(4) secretion in these cells, 3) provide the first evidence that p53 suppress proliferation of ovarian cells, 4) provide the first evidence that p53 is involved in the control of ovarian peptide hormone (OT) and prostaglandin (PGF and PGE) secretion, and 5) suggest that p53 can modulate, but probably not mediate, the effects of ghrelin and FSH on the ovary.

Some endocrine traits of transgenic rabbits. II. Changes in hormone secretion and response of isolated ovarian tissue to FSH and ghrelin.

In the present in vitro experiments we examined FSH- and ghrelin-induced changes in ovarian hormone secretion by transgenic rabbits. Fragments of ovaries isolated from adult transgenic (carrying mammary gland-specific mWAP-hFVIII gene) and non-transgenic rabbits from the same litter were cultured with and without FSH or ghrelin (both at 0, 1, 10 or 100 ng/ml medium). The secretion of progesterone (P4), estradiol (E2) and insulin-like growth factor I (IGF-I) was assessed by RIA. It was observed that ovaries isolated from transgenic rabbits secreted much less P4, E2 and IGF-I than the ovaries of non-transgenic animals. In control animals FSH reduced E2 (at doses 1-100 ng/ml medium) and IGF-I (at 1-100 ng/ml), but not P4 secretion, whereas ghrelin promoted P4 (at 1 ng/ml) and IGF-I (at 100 ng/ml), but not E2 output. In transgenic animals, the effects were reversed: FSH had a stimulatory effect on E2 (at 100 ng/ml) and ghrelin had an inhibitory effect on P4 (at 10 ng/ml). No differences in the pattern of influence of FSH on P4 and IGF-I and of ghrelin on E2 and IGF-I were found between control and transgenic animals. The present observations suggest that 1) both FSH and ghrelin are involved in rabbit ovarian hormone secretion, 2) transgenesis in rabbits is associated with a reduction in ovarian secretory activity, and 3) transgenesis can affect the response of ovarian cells to hormonal regulators.

The effect of obestatin on porcine ovarian granulosa cells.

The aim of our in vitro experiments was to investigate the role of obestatin, a newly discovered metabolic hormone produced in the stomach and other tissues, in the direct control of ovarian cell proliferation, apoptosis and secretion. Porcine granulosa cells were cultured in the presence of obestatin (0, 1, 10 and 100ng/ml medium). The expression of intracellular peptides associated with proliferation (PCNA, cyclin B1, MAP kinase), as well as markers of apoptosis (Bax, p53, Caspase 3), were detected using immunocytochemistry and Western immunoblotting. Secretion of progesterone (P4), testosterone (T) and estradiol (E2) was measured by EIA. Addition of obestatin (1-100ng/ml) to the culture medium significantly stimulated the expression of PCNA and resulted in an increase in expression of cyclin B1 and MAPK. It also significantly increased the percentage of cells containing the apoptotic and anti-proliferating peptides p53, Caspase 3 and Bax. At 10 and 100ng/ml, obestatin promoted the secretion of P4, but not T or E2. Our results are the first demonstration that obestatin directly controls porcine ovarian cell functions: it can stimulate proliferation (accumulation of rPCNA, cyclin B1 and MAPK), apoptosis (expression of p53, Caspase 3 and Bax) and the secretion of progesterone.

Ahmed glaucoma drainage implant surgery in the management of refractory uveitic glaucoma: Long-term follow up. / Implante de válvula de Ahmed para el manejo del glaucoma uveítico refractario: seguimiento a largo plazo.

OBJECTIVE: To examine the long-term efficacy, safety and complications of Ahmed glaucoma drainage implant surgery in patients with refractory uveitic glaucoma. METHODS: Retrospective review of consecutive cases of patients with refractory uveitic glaucoma who underwent Ahmed glaucoma drainage implant surgery between 2004-2014. Demographic characteristics of the study population, visual acuity, intraocular pressure (IOP), number of antiglaucoma medications and operative and postoperative complications were recorded. Complete success was defined as IOP≥5 and ≤18mmHg without any medication, as qualified success if IOP≤18mmHg with one or more medications. Patients with less than 12 months of follow-up were excluded. RESULTS: 21 patients (26 eyes) were included. The mean postoperative follow-up was 53.5±31 months. Eight eyes (30%) had at least one previously failed glaucoma surgery. IOP was reduced from a mean of 30.0mmHg to 14.0mmHg at the last follow-up visit (P<.001). The number of IOP-lowering medications was reduced from a median of 2.9 preoperatively to 1.1 at the last follow-up (P<.001). Overall, 7 eyes (27%) were classified as complete success, 13 eyes (50%) were considered as qualified success, and 6 eyes (23%) met the criteria for failure. The most common postoperative complication was hypertensive phase in 12 eyes (46%). Kaplan-Meier life-table analysis showed a cumulative probability of success after Ahmed glaucoma valve implantation of 65% at 84 months. CONCLUSIONS: Ahmed glaucoma drainage implant surgery may be considered a long-term effective and safety surgical option for patients with refractory uveitic glaucoma.