Rapid quasi-periodic oscillations in the relativistic jet of BL Lacertae.

Blazars are active galactic nuclei (AGN) with relativistic jets whose non-thermal radiation is extremely variable on various timescales1-3. This variability seems mostly random, although some quasi-periodic oscillations (QPOs), implying systematic processes, have been reported in blazars and other AGN. QPOs with timescales of days or hours are especially rare4 in AGN and their nature is highly debated, explained by emitting plasma moving helically inside the jet5, plasma instabilities6,7 or orbital motion in an accretion disc7,8. Here we report results of intense optical and γ-ray flux monitoring of BL Lacertae (BL Lac) during a dramatic outburst in 2020 (ref. 9). BL Lac, the prototype of a subclass of blazars10, is powered by a 1.7 × 108 MSun (ref. 11) black hole in an elliptical galaxy (distance = 313 megaparsecs (ref. 12)). Our observations show QPOs of optical flux and linear polarization, and γ-ray flux, with cycles as short as approximately 13 h during the highest state of the outburst. The QPO properties match the expectations of current-driven kink instabilities6 near a recollimation shock about 5 parsecs (pc) from the black hole in the wake of an apparent superluminal feature moving down the jet. Such a kink is apparent in a microwave Very Long Baseline Array (VLBA) image.

The excitation of solar-like oscillations in a δSct star by efficient envelope convection.

Delta Scuti (δSct) stars are opacity-driven pulsators with masses of 1.5-2.5 M⊙, their pulsations resulting from the varying ionization of helium. In less massive stars such as the Sun, convection transports mass and energy through the outer 30 per cent of the star and excites a rich spectrum of resonant acoustic modes. Based on the solar example, with no firm theoretical basis, models predict that the convective envelope in δSct stars extends only about 1 per cent of the radius, but with sufficient energy to excite solar-like oscillations. This was not observed before the Kepler mission, so the presence of a convective envelope in the models has been questioned. Here we report the detection of solar-like oscillations in the δSct star HD187547, implying that surface convection operates efficiently in stars about twice as massive as the Sun, as the ad hoc models predicted.

AMPA receptor subunit 1 (GluR-A) knockout mice model the glutamate hypothesis of depression.

Recent evidence indicates that glutamate homeostasis and neurotransmission are altered in major depressive disorder, but the nature of the disruption and the mechanisms by which it contributes to the syndrome are unclear. Glutamate can act via AMPA, NMDA, or metabotropic receptors. Using targeted mutagenesis, we demonstrate here that mice with deletion of the main AMPA receptor subunit GluR-A represent a depression model with good face and construct validity, showing behavioral and neurochemical features of depression also postulated for human patients. GluR-A(-/-) mice display increased learned helplessness, decreased serotonin and norepinephrine levels, and disturbed glutamate homeostasis with increased glutamate levels and increased NMDA receptor expression. These results correspond well with current concepts regarding the role of AMPA and NMDA receptors in depression, postulating that compounds that augment AMPA receptor signaling or decrease NMDA receptor functions have antidepressant effects. GluR-A(-/-) mice represent a model to investigate the pathophysiology underlying the depressive phenotype and to identify changes in neural plasticity and resilience evoked by the genetic alterations in glutamatergic function. Furthermore, GluR-A(-/-) mice may be a valuable tool to study biological mechanisms of AMPA receptor modulators and the efficacy of NMDA antagonists in reducing behavioral or biochemical changes that correlate with increased helplessness.

Chronic fluoxetine administration inhibits extracellular signal-regulated kinase 1/2 phosphorylation in rat brain.

Accumulating evidence indicates that antidepressants alter intracellular signalling mechanisms resulting in long-term synaptic alterations which probably account for the delay in clinical action of these drugs. Therefore, we investigated the effects of chronic fluoxetine administration on extracellular signal-regulated kinase (ERK) 1 and 2, a group of MAPKs that mediate signal transduction from the cell surface downstream to the nucleus. Our data demonstrate that 3-week fluoxetine treatment resulted in long-lasting reduction of phospho-ERK 1 and 2. Such an effect depends on the length of the treatment given that no changes were observed after a single drug injection or after 2 weeks of treatment and it is region specific, being observed in hippocampus and frontal cortex but not in striatum. Finally, phospho-ERK 1 and 2 were differently modulated within nucleus and cytosol in hippocampus but similarly reduced in the same compartments of the frontal cortex, highlighting the specific subcellular compartmentalization of fluoxetine. Conversely, imipramine did not reduce the hippocampal phosphorylation of both ERK subtypes whereas it selectively increased ERK 1 phosphorylation in the cytosolic compartment of frontal cortex suggesting a drug-specific effect on this intracellular target. These results point to modulation of phosphorylation, rather than altered expression, as the main target in the action of fluoxetine on this pathway. The reduction of ERK 1/2 function herein reported may be associated with the therapeutic effects of fluoxetine in the treatment of depression.

Development and characterization of potato-Solanum brevidens chromosomal addition/substitution lines.

Solanum brevidens is a wild diploid potato species possessing high levels of resistances to several major potato diseases. We previously developed fertile somatic hybrids between S. brevidens and the cultivated potato (Solanum tuberosum) in order to introgress disease resistances from this wild species into potato. A series of backcross progenies was developed from a hexaploid somatic hybrid A206. Using a combination of S. brevidens-specific randomly amplified polymorphic DNA (RAPD) markers and a sequential genomic in situ hybridization (GISH) and fluorescence in situ hybridization (FISH) technique, we identified all 12 S. brevidens chromosomes in the backcross progenies. Seven potato-S. brevidens monosomic chromosome addition lines (chromosomes 1, 3, 4, 5, 8, 9 and 10) and one monosomic substitution line (chromosome 6) were identified, and the remaining four S. brevidens chromosomes (2, 7, 11, and 12) were included in two other lines. These chromosomal addition/substitution stocks provide valuable tools for potato cytogenetic research, and can be used to introgress disease resistances from S. brevidens into potato.

Association between lesional or non lesional S. aureus strains from patients with impetigo and exfoliative toxin production. No association with SmaI PFGE patterns.

Contrasting data are reported in the literature on the percent positivity rates (13.5%-100%) of exfoliative toxin (ET) production by S. aureus strains isolated from impetigo patients in Japan and in France. In the present study, by means of a recently available latex-test, toxin-A (ETA) or toxin-B (ETB) production was found in 67.6% of the 34 S. aureus strains isolated from 19 lesional (63.2%) and 15 non-lesional (nose or pharynx, 73.3%) areas of patients with impetigo (with no significant difference between the lesional and non-lesional isolates). ETA + ETB were produced by 44.1% of the strains, while 32.4% were non-producers. In contrast, the percent positivity rate observed in 40 [20 lesional and 20 non-lesional (nose or pharynx)] strains isolated in patients with atopic dermatitis was 15.0% (p < 0.001 both for the lesional and non-lesional strains versus impetigo, with no significant difference between lesional and non lesional strains). Finally, 26 strains from other types of specimens (abscesses, hemocultures, urine, central venous catheters, bronchoalveolar lavages) showed an 11.5% production rate of ETA or ETB (p < 0.001 versus impetigo strains, no significance versus atopic dermatitis). These data point to a significant association between exfoliative toxin production and S. aureus strains isolated in impetigo, both in lesional areas and in nasal/pharyngeal reservoirs. An attempt to correlate SmaI pulsed-field gel electrophoresis (PFGE) restriction patterns and exfoliative toxin production showed no significant association in either group.

Toxic shock syndrome due to group C streptococci. A case report.

BACKGROUND: Streptococcal toxic shock-like syndrome is a life-threatening illness which is on the increase. In early reports, only group A beta-hemolytic streptococcus was associated with the disease, but recent evidence indicates non-A streptococci groups are also involved. OBSERVATIONS: We describe the first reported case of streptococcal toxic shock-like syndrome caused by a group C strain in Italy. Prior to the disease, the patient, a 46-year-old man, had been in good health and had only a 3-day history of sore throat, low grade fever, vomiting, diarrhea, and myalgia before admission. Initially, diagnosis was based only on clinical evidence: shock, multiorgan failure, profound hypothermia, and no apparent signs of infection. Toxic cardiomyopathy was also present. RESULTS: Positive throat swab and blood culture confirmed a "definite case" following established criteria. Anamnesis showed a diagnosis of monoclonal gammopathy. Antibiotic treatment was begun immediately on admission of the patient, who was discharged 20 days later in good health. CONCLUSIONS: This case illustrates how an early diagnosis and prompt antibiotic therapy can determine a more favorable outcome.

Sequential biochemotherapy for metastatic colorectal cancer using fluorouracil, folinic acid, thymopentin and interleukin-2: clinical and immunological effects.

BACKGROUND: A phase II study was performed to evaluate the clinical and immunological effects of a regimen of fluorouracil (5-FU) and folinic acid (FA) combined with thymopentin (TP-5) and interleukin-2 (IL-2) in the treatment of patients with metastatic colorectal cancer. PATIENTS AND METHODS: Forty-five evaluable patients with measurable colorectal cancer and no prior therapy for metastatic disease were treated with 5-FU 400 mg/m2/d and FA 200 mg/m2/d i.v. on days 1-5, TP-5 50 mg s.c. on days 8-11, and IL-2 9 MU/m2 s.c. twice daily on days 12-16. Cycles were repeated at 4-week intervals if toxicity had resolved. Immunological changes were evaluated in 13 patients and compared with a well matched series of 13 patients treated with the same regimen without TP-5. RESULTS: Two complete responses and 17 partial responses were seen (42%; 95% confidence interval, 28% to 56%). Fifteen patients (33%) had stable disease. The median time to progression was 8.5 months and the median survival 13 months. Treatment was reasonably well tolerated, and there was no overlapping toxicity or interference between chemotherapy and biotherapy. Hematological and immunological changes during treatment were qualitatively similar to those expected with IL-2 +/- chemotherapy. Quantitatively, significant changes (higher levels of IL-2, CD25 and IFN-gamma, and lower levels of sIL-2R) were observed in patients given TP-5. CONCLUSION: The combination of 5-FU + FA and TP-5 + IL-2 is effective in advanced colorectal cancer with acceptable toxicity. Immunological data suggest that TP-5 may modulate the action of IL-2 in the clinical setting. However, improved treatment approaches are needed, and the interactions between thymic hormones and cytokines should be further explored.

Biochemotherapy with thymosin alpha 1, interleukin-2 and dacarbazine in patients with metastatic melanoma: clinical and immunological effects.

BACKGROUND: DTIC and interleukin-2 (IL-2), as single agents, have a limited anti-tumor activity in patients with metastatic melanoma. Experimentally, thymosin alpha 1 (TA1) may modulate the action of IL-2. We investigated the clinical and immunological effects of a combination with these three agents. PATIENTS AND METHODS: Forty-six patients with measurable metastatic melanoma were treated with DTIC 850 mg IV on day 1, TA1 2 mg s.c. on days 4 to 7, and IL-2 18 MU/m2/d by continuous intravenous infusion on days 8 to 12. Cycles were repeated every 3 weeks. RESULTS: Objective responses were obtained in 15 (36%) of 42 evaluable patients (CI at 95%: 22%-50%). Two patients experienced complete responses, and stable disease was observed in five. The median time to progression was 5.5 months and median survival was 11 months. Side effects were predominantly caused by IL-2. Treatment was tolerated reasonably well, and there was no overlapping toxicity or interference between chemotherapy and biotherapy. Baseline sCD4 levels seem to correlate to tumor burden. Patients benefiting from treatment had lower sCD4 and higher sCD8 than did progressing patients. CONCLUSIONS: The combination of DTIC + TA1 + IL-2 is active in the treatment of advanced melanoma, with acceptable toxicity. However, even more active regimens are needed, and the interactions between thymic hormones and cytokines should be further explored.

Epidural sufentanil for postoperative analgesia: dose-response in patients recovering from major gynecologic surgery.

To determine the lowest effective dose of epidural sufentanil given for analgesia, 41 patients undergoing elective abdominal gynecologic surgery during continuous epidural anesthesia (lidocaine 2%) were randomly assigned to one of four postoperative treatment groups. Patients received an epidural bolus of either 25 (group A), 40 (group B), 55 (group C), or 70 micrograms (group D) sufentanil in 10 mL of saline. They were evaluated for the next 8 h using a 10-cm visual analogue scale. Except for two individuals in group A, all patients achieved a visual analogue scale score of 1 cm or less during the study interval. The onset of analgesia was most rapid in the two higher dose groups (A vs C and D; P less than 0.05). Pairwise comparison between groups showed a significant difference in the time needed to achieve maximum pain relief between the lowest and highest treatment groups (A vs D; P less than 0.05). Duration of analgesia was also significantly longer in groups C and D than in group A (208.0 +/- 21.1 and 224.0 +/- 14.7 vs 140.0 +/- 10.7 min; P less than 0.05). There were no differences among groups with regard to mean respiratory rate, level of sedation, 24-h narcotic requirements, or incidence of nausea, vomiting, and pruritus (P = NS). A single patient in group D suffered profound respiratory depression within seconds of administration. We conclude that, in patients recovering from lower abdominal surgery, a single 40-55-micrograms epidural bolus of sufentanil provides 3-3.5 h of effective analgesia, and that larger doses are not warranted.

[Clonidine and postoperative shivering]. / La clonidina nel brivido postoperatorio.

Clonidine was clinically evaluated to suppress postoperative shivering in 60 patients who had undergone anesthesia for general, thoracic and vascular surgery. The study was carried out in double blind conditions with comparison of two doses (75 and 150 micrograms) of clonidine, one dose of methylphenidate, and one dose of saline, as control group. The level of inhibition (Goldfarb scale), haemodynamics and temperature were studied. In conclusion, the methylphenidate is drug first choice for postoperative shivering, but clonidine inhibits postoperative shivering without haemodynamic and temperature variations (75 micrograms).

[Clinical evaluation of propofol-ketamine anesthesia in general surgery]. / Valutazione clinica dell'anestesia con propofol-ketamina in chirurgia generale.

The combinations propofol-ketamine vs propofol-fentanyl in absence of N2O was compared in 60 patients undergoing abdominal surgery. The results show that ketamine and fentanyl provide a good analgesia in the absence of N2O and that ketamine offers better haemodynamic control.

[Efficacy of the disinfection of fiber endoscopes]. / Studio sulla efficacia della disinfezione di fibroendoscopi.

The validity of routine disinfection of gastrointestinal fibroscopes is reported. The Authors present their work based on 204 tests performed on gastroscopes and colonoscopes after manual disinfection performed by skilled nurses. All the instruments were kept in a 1:16 solution of glutaraldehyde-phenate for 10 minutes. Microbiological tests were performed half on sterile solution flushed on the outer part of the endoscope and half into the bioptic channel. Different groups of tests are reported. When strict asepsis was observed in handling the endoscopes all tests demonstrated to be sterile. When the endoscopes were handled as in usual routine, i.e. without sterile gloves and so on, 20% of the tests showed the presence of bacteria: these were only of types present in the environment. No real pathogens or antibiotic resistant strains were observed. The total disinfection procedure showed to be easy and quick to perform. No allergic or toxic reactions were observed. The importance of this procedure as a routine one in all endoscopy units is stressed considering also that literature data demonstrate the efficacy of glutaraldehyde-phenate against hepatitis and AIDS viruses.

Dose and schedule effects of cisplatin on the related acute iron changes.

To investigate the relationships between cisplatin and the related erythropoiesis impairment, 14 patients receiving very-high-dose cisplatin (40 mg/m2/day for 5 days) and 17 patients receiving standard-high-dose cisplatin (either a single dose of 100 or 20 mg/m2/day for 5 days) entered this study. Iron, ferritin, hemoglobin, and reticulocyte levels were evaluated before, 4 and 6 days after each course of cisplatin. A complete blood count was obtained weekly. During the 1st week after chemotherapy, iron and ferritin levels significantly increased, and the reticulocyte count decreased. Iron changes depend on the cisplatin dose, but are not related to the different schedules employed. The severity of subacute anemia was found to be dependent on the cisplatin dose administered and on hemoglobin pretreatment levels. Some relationships between cisplatin, iron changes, and the subacute hemoglobin decrease are described.

Chemoprophylaxis of bacterial infections in granulocytopenic cancer patients using norfloxacin.

Sixty-five cancer patients pretreated with chemo or radiotherapy, with granulocytopenia less than 1000/mm3 and without fever, were entered into this study: 30 of them were submitted to prophylaxis with norfloxacin while the remaining 35 patients were used as a control group. 20% of the treated subjects versus 68.6% of the controls presented a subsequent infection (P less than 0.001), the lung representing the most frequent site of the infectious disease in both groups (3/6 and 14/24 respectively). These data strongly suggest the use of norfloxacin as an effective prophylactic drug in nonfebrile, granulocytopenic cancer patients, especially as far as gram-negative infections are concerned. Because of the high prevalence of lung cancer in the patients of our study, and a related prevalence of lung infections, at the present time, a wider use of this antibiotic in every kind of solid tumor cannot be generalized.

[Colorimetric determination of plasma vitamin C: comparison between 2,4-dinitrophenylhydrazine and phosphotungstic acid methods (author's transl)]. / Confronto tra i metodi della 2,4-dinitrofenilidrazina e dell'acido fosfotungstico per la determinazione colorimetrica della vitamina C nel plasma.

The evaluation of a recently published colorimetric method for plasma ascorbic acid determination, using phosphotungstic acid (PTA), was performed by comparison with the largely employed 2,4-dinitrophenylhydrazine (DNPH) procedure. The method has been evaluated according to International Federation of Clinical Chemistry (I.F.C.C.) recommendations. In particular, calibration procedures have been performed and precision, accuracy, linearity, specificity and sensitivity have been studied in biological samples. Linear regression analysis indicates that the two methods do not correlate completely. The PTA method shows a better recovery. The PTA method shares with the DNPH procedure a poor precision at low concentrations of vitamin C in plasma such as to make results less reliable at the clinically significative levels.

[Association between viral infection and pleuropericarditis: study of a case list of pleurisy and pericarditis]. / Associazione tra infezione virale e pleuro-pericarditi: studio di una casistica di pleuriti e pericarditi.

The Authors report a study on a group of 47 patients affected by serositis (pleuritis, pericarditis, pleuro-pericarditis) of suspected viral origin. Two serum samples were taken from each patient at different times and were tested with many viral antigens by the complement fixation technique. The discussion is carried out on the lines followed by the majority of people in giving importance to their viral etiology and the viruses involved as agents of serositis are reported. In the present study 18 patients (38%) showed a significant rise of antibodies for viral antigens and therefore their disease might be due to viral etiology: 5 influenza viruses, 1 parainfluenza, 1 coxsackie, 1 RSV, 3 mumps virus, 5 CMV, 1 adenovirus.