Induction of partial protection in mice after oral administration of Lactococcus lactis producing Brucella abortus L7/L12 antigen.

The Brucella abortus ribosomal protein L7/L12 is an immunodominant antigen and an interesting candidate for the development of oral live vaccines against brucellosis. Here, a recombinant Lactococcus lactis strain producing L7/L12 under the control of nisin inducible promoter was orally administered to BALB/c mice. Significant levels of anti-L7/L12 specific IgA detected in feces revealed an induced local humoral immune response. However, serum analysis did not reveal any anti-L7/L12 antibodies suggesting the absence of a systemic response. Nevertheless, the vaccinated mice showed a partial protective immunity against B. abortus virulent strain (S2308) challenged by intraperitoneal inoculation.     

An assessment of fructose-1,6-bisphosphate as an antimicrobial and anti-inflammatory agent in sepsis.

Tissue lesion mechanisms provoked by sepsis include the infectious process, inflammation, and cellular energy deficit. We chose to test fructose-1,6-bisphosphate (FBP) because of its possible anti-inflammatory and antimicrobial actions. Wistar rats were used and divided into three experimental groups: a control group (n=10), in which a capsule was introduced into the peritoneum of the animals; a septic group (n=10), in which a capsule containing non-sterile fecal matter was introduced together with Escherichia coli (1.5 x 10(9)CFU); and a septic group treated with FBP 500 mg/kg (n=10). The blood cell tests revealed that levels of leukocytes increased significantly in the septic group when compared to both the septic group treated with FBP and the control group. The blood cultures were 100% positive in both the septic group and the septic group treated with bisphosphorylated sugar. The antibiogram only revealed an inhibitory halo in the case of the antibiotic ampicillin, there was no such indication for FBP. The anti-inflammatory power of FBP remained at 60% for 5 h in the rats that received the carrageenan injection. What is more, the sugar reduced the levels of ionic calcium in relation to the control group. This data proves the validity of using FBP in the treatment of sepsis, possibly due to its anti-inflammatory rather than antimicrobial action.     

Skp2 protein expression in soft tissue sarcomas.

BACKGROUND: p45 S phase kinase-associated protein-2 (p45(skp2)), a member of the F-box family of proteins, is an important component of the Skp1-Cullin-F-box protein (SCF) ubiquitin-ligase complex (SCF(skp2)). The latter has been implicated in the ubiquitination and degradation of p27(kip1) (p27) and G(1)-S cell cycle progression. The expression and prognostic role of Skp2 in a large series of soft tissue sarcomas has not been previously investigated. METHODS: Clinicopathologic features and immunohistochemical expression of Skp2, p27, and Ki-67 proteins were studied in 182 cases of soft tissue sarcomas (American Joint Committee on Cancer stages II and III). Survival analyses were performed using the Kaplan-Meier method and the Cox regression model. RESULTS: The male to female ratio was 1.2:1, and the median age at the diagnosis was 53 years. The tumors were predominantly located in the lower extremities (n = 163; 90%) and had a median size of 9 cm. High Skp2 expression (> or = 10% of the cells) was identified in 68 tumors (37%), and was correlated with high grade histology (P =.002) and Ki-67 proliferative index (r = 0.44; P <.0001), but not with p27 expression (r = -0.02; P =.80). By univariate analysis, high Skp2 expression was associated with decreased metastasis-free, disease-free, and overall survival. In a multivariate model, high Skp2 expression was an independent predictor for decreased local recurrence-free, disease-free, and overall survival. CONCLUSION: These results indicate that Skp2 expression is associated with cell proliferation and a worse prognosis in soft tissue sarcomas. The lack of an inverse correlation between Skp2 and p27 suggests that additional molecular events associated with either Skp2 expression or p27 proteolysis may be operating in these tumors.     

How to organize gynecologic oncology in the future: Results of an internationalquestionnaire

Vergote IB, de Oliveira CF, Dargent D. How to organize gynecologic oncologyin the future: Results of an international questionnaire. Int J GynecolCancer 1997; 7: 368–375.
A questionnaire was sent to 93 gynecologic oncologists from 54 countriesabout the way in which gynecologic oncology was organized in their country, orif the (sub)speciality wasnot yet recognized, how they thought it should be organized. The questionnairewas answered by 64 persons from 42 different countries. The subspecialty wasrecognised in 17 (41%) of the countries. Fifty-five respondents (86%) thought thatgynecologic oncology should be a subspecialty of obstetrics and gynecology. Themedian duration of the gynecologiconcologic fellowship program was 30 months. Diagnosis and surgery accounted forabout 58% of the duration of the program. In 52% of the answersfrom countries with boardcertification, the fellows had to pass a theoretical and practical examination,and in addition 22% of the candidates had to defend a thesis to qualifyfor certification.Training centers in countries that recognized gynecologic oncology had amedian number of 142 new cases per year (for 1 fellow). The median number ofgynecologic oncologogistsand fellows per 10⁽⁷⁾ inhabitants in countries with boardcertification in gynecologic oncology was 42 and 6, respectively. Finally, theimportant role of internationalsocieties (like the International Gynecologic Cancer Society and the EuropeanSociety of Gynaecological Oncology) in supporting the countries withoutrecognized GynecologicOncology was stressed by the respondents. The setting up of internationalstandards for training programs, training centers, board certification, and theorganization ofinternational exchange programs for fellows seemed to be equally important,according to the questionnaire responses.     

Retinal ganglion cells in the South American opossum (Didelphis aurita)

By using the Golgi technique, the authors investigated the morphology of ganglion cells in the retinas of South American opossums. In flat-mount preparations of the retinas, cell bodies, entire dendritic fields, and the stratification level of ganglion cells were studied. Fractal dimensions of dendritic trees, an objective quantitative measure of morphological complexity, were included as a morphological parameter of classification. Based on these characteristics, nineteen types of ganglion cells were described. A great number of opossum ganglion cell types had dendrites stratifying in both sublaminae of the inner plexiform layer (IPL) in five different ways (S1-S3 [G9], S1-S4 [G17 and G22], S2/S3 [G19], S2-S4 [G15, G16, G21 and G221, and S2-S5 [G61), and only two types (G8, and G10) showed narrow field dendritic trees ramifying in S4 only. Morphological types of opossum ganglion cells were compared to their counterparts in cat retina. The distribution pattern of large cell bodies on the ganglion cell layer was analyzed employing the Nissl staining method, immunocytochemistry for neurofilaments, and the reduced silver neurofibrillar staining method. The results showed a random pattern of distribution.     

The role of associated injuries on outcome of blunt trauma patients sustaining pelvic fractures

In order to identify the prognostic factors and to evaluate the impact of associated injuries in the outcome of patients with pelvic fractures, a retrospective review of the medical records of patients admitted with a pelvic fracture during a 42-month period was carried out. Demographic data, the mechanism of injury, the physiologic status on admission, associated injuries, pelvic fracture classification, complications and mortality were analysed. One hundred and three patients were included in the study. Fifty-nine were male, and the mean age was 34. The mean Revised Trauma Score (RTS) and Injury Severity Score (ISS) were 7.1 and 20, respectively. Pedestrian vs vehicle (59%), was the most frequent mechanism of injury. Twenty patients died (19%) most frequently due to "shock". Complications developed in 37 patients (36%), pneumonia being the most frequent. Age greater than 40 years (p=0.02), "shock" upon admission (p=0.002), a Glasgow Coma Scale (GCS)<9, Head AIS>2 (p<0. 001), Chest AIS>2 (p=0.007), and abdominal AIS>2 (p=0.03) all correlated with increased mortality. No correlation between pelvic fracture classification or fracture stability with mortality was observed. The outcome of patients with pelvic fractures due to blunt trauma correlates with the severity of associated injuries and physiological derangement on admission rather than with characteristics of or the type of fracture.     

Transdermal nitroglycerine enhances spinal neostigmine postoperative analgesia following gynecological surgery

BACKGROUND: Intrathecal neostigmine causes analgesia by inhibiting the breakdown of acetylcholine. Experimental data suggest that the production of endogenous nitric oxide is necessary for tonic cholinergic inhibition of spinal pain transmission. The purpose of this study was to determine whether association of transdermal nitroglycerine would enhance analgesia from a low dose of intrathecal neostigmine in patients undergoing gynecologic surgery during spinal anesthesia. METHODS: Forty-eight patients were randomized to one of four groups. Patients were premedicated with use of 0.05-0.1 mg/kg intravenous midazolam and received 15 mg bupivacaine plus 1 ml test drug intrathecally (saline or neostigmine, 5 microgram). Twenty to 30 min after the spinal puncture, a transdermal patch of either 5 mg nitroglycerin or placebo was applied. The control (Con) group received spinal saline and transdermal placebo. The neostigmine group received spinal neostigmine and transdermal placebo. The nitroglycerin group received spinal saline and a transdermal nitroglycerine patch. Finally, the neostigmine-nitroglycerin group received spinal neostigmine and transdermal nitroglycerine. Pain and adverse effects were evaluated using a 10-cm visual analog scale. RESULTS: Patients in the groups were similar regarding age, weight, height, and American Society of Anesthesiologists status. Sensory level to pin prick at 10 min, surgical duration, anesthetic duration, and visual analog scale score for pain at the time of administration of first rescue medication were statistically the same for all groups. The time to administration of first rescue analgesic (min) was longer in the neostigmine-nitroglycerin group (550 min; range, 458-1,440 min; median, 25-75th percentile) compared with the other groups (P < 0.001). The neostigmine-nitroglycerin group required fewer rescue analgesics in 24 h than did the control group (P < 0.0005), whereas the neostigmine group required less analgesics compared with the control group (P < 0.02). The incidence of perioperative adverse effects (nausea, vomiting, headache, back pain) was similar among groups (P > 0.05). CONCLUSION: Although neither intrathecal 5 microgram neostigmine alone nor transdermal nitroglycerine alone (5 mg/day) delayed the time to administration of first rescue analgesics, the combination of both provided an average of 14 h of effective postoperative analgesia after vaginoplasty, suggesting that transdermal nitroglycerin and the central cholinergic agent neostigmine may enhance each other's antinociceptive effects at the dose studied.     

Neurobehavioral and genotoxic aspects of rosmarinic acid.

Rosmarinic acid is a naturally occurring hydroxylated compound. It is present in many plants, for example, it occurs in Artemisia capillaris, Calendulla officinalis, Melissa officinalis, Salvia officinalis and in other several plant families. It also shows a number of interesting biological activities, e.g. antiviral, antibacterial, antiinflammatory and antioxidant. The aim of the present study was to investigate the effect of the i.p. administration of rosmarinic acid (1, 2, 4 or 8 mg kg(-1)) on elevated plus-maze, step-down inhibitory avoidance and open field task in rats. In addition, we evaluated its genotoxic effect on brain tissue using the comet assay. Rosmarinic acid (2 and 4 mg kg(-1)) increased the number of entries in the open arms, suggesting an anxiolytic-like activity when used in lower doses, without affecting the short-term memory (STM) and long-term memory (LTM) retention on inhibitory avoidance task. Eight milligrams per kilograms of this acid was enough to increase the locomotion and motivation of the animals, but not 1, 2 or 4 mg kg(-1), suggesting that in lower doses, this compound can produce anxiolytic-like effect without exerting locomotor alterations or DNA damage in brain tissue.     

Effect of chronic exposure to aluminium on isoform expression and activity of rat (Na+/K+)ATPase.

The ability of aluminum to inhibit the (Na(+)/K(+))ATPase activity has been observed by several investigators. The (Na(+)/K(+))ATPase is characterized by a complex molecular heterogeneity that results from the expression and differential association of multiple isoforms of both catalytic (alpha) and regulatory (beta) subunits. For instance, three main alpha (alpha(1), alpha(2) and alpha(3)) and three beta (beta(1), beta(2) and beta(3)) subunit isoforms exist in vertebrate nervous tissue, whereas only alpha(1) and beta(1) have been identified in kidney. However, no studies have focused on determining the change in (Na(+)/K(+))ATPase isoforms caused by chronic exposure to aluminum and its relation with aluminum toxicity. In this study, adult male Wistar rats were submitted to chronic dietary AlCl(3) exposure (0.03 g/day of AlCl(3) for 4 months), and the activity and protein expression of (Na(+)/K(+))ATPase isozymes were studied in brain cortex synaptosomes and in kidney homogenates. The intracellular levels of adenine nucleotides, plasma membrane integrity, and aluminum accumulation were also studied in brain synaptosomes. Aluminum accumulation upon chronic dietary AlCl(3) administration significantly decreased the (Na(+)/K(+))ATPase activity measured in the presence of nonlimiting Mg-ATP concentrations, without compromising protein expression of alpha-subunit isoforms in brain and kidney. Aluminum-induced synaptosomal (Na(+)/K(+))ATPase inhibition was due to a reduction in the activity of isozymes containing alpha(1)-alpha(2) and alpha(3)-subunits. The onset of enzyme inhibition was accompanied by a decrease of the (Na(+)/K(+))ATPase sensitivity to submicromolar concentrations of ouabain, and it preceded major damage in plasma membrane integrity and energy supply, as revealed by the analysis of lactate dehydrogenase leakage and endogenous adenine nucleotides. The data suggest that, during chronic dietary exposure to AlCl(3), brain (Na(+)/K(+))ATPase activity drops, even if no significant alterations of catalytic subunit protein expression, cellular energy depletion, and changes in cell membrane integrity are observed. Implications regarding underlying mechanisms of aluminum neurotoxicity are discussed.