Changes in cutaneous and body temperature during and after conditioned fear to context in the rat

Infrared thermography was used to image changes in cutaneous temperature during a conditioned fear response to context. Changes in heart rate, arterial pressure, activity and body (i.p.) temperature were recorded at the same time by radio-telemetry, in addition to freezing immobility. A marked drop in tail and paws temperature (-5.3 and -7.5 degrees C, respectively, down to room temperature), which lasted for the entire duration of the response (30 min), was observed in fear-conditioned rats. In sham-conditioned rats, the drop was on average half the magnitude and duration. In contrast, temperature of the eye, head and back increased (between + 0.8 and + 1.5 degrees C), with no difference between the two groups of rats. There was a similar increase in body temperature although it was slightly higher and delayed in the fear-conditioned animals. Finally, ending of the fear response was associated with a gradual decrease in body temperature and a rebound increase in the temperature of the tail (+ 3.3 degrees C above baseline). This study shows that fear, and to some extent arousal, evokes a strong cutaneous vasoconstriction that is restricted to the tail and paws. This regionally specific reduction in blood flow may be part of a preparatory response to a possible fight and flight to reduce blood loss in the most exposed parts of the rat's body in case of injury. The data also show that the tail is the main part of the body used for dissipating internal heat accumulated during fear once the animal has returned to a safe environment.     

Lower extremity amputations in diabetic patients: a case-control study

OBJECTIVE: Lower extremity amputation is an increasing problem among diabetic patients and an important public health problem. The study purpose was to identify factors associated with lower extremity amputation. METHODS: A matched case-control study was carried out among diabetic patients. Cases were selected in public health programs of the city of S?o Paulo, Brazil. One hundred and seventeen cases of diabetics with lower extremity amputation were compared to 234 controls of diabetics without amputation, matched by sex, age, and duration of disease. Sociodemographic variables, life habits (smoking and alcohol drinking), clinical aspects, and health education in diabetes were included. Univariate analyses and conditional logistic regression method were applied to data. RESULTS: Data showed evidence of association for: smoking, last glucose test > or = 200 mg/dl, presence of peripheral somatic neuropathy and vibratory perception (tuning fork 128 Hz), and peripheral vascular disease. Diabetes treatment and attending nursing appointments for diabetes education were important factors for preventing lower extremity amputation in diabetic patients. CONCLUSIONS: The knowledge of determinants and intervening factors for this condition will lead to cost reduction and better quality of care delivered in public health services.     

Protein synthesis, PKA, and MAP kinase are differentially involved in short- and long-term memory in rats

We studied the involvement of hippocampal protein synthesis-, PKA-, and MAP kinase-dependent processes in short- (STM) and long-term memory (LTM) for inhibitory avoidance task. Fifteen minutes before or immediately after training rats received intrahippocampal infusions of vehicle, the protein synthesis inhibitor anisomycin, the PKA inhibitor Rp-cAMPs or the MAPKK inhibitor PD098059. The results show that STM recruits PKA and MAPK, whereas, LTM depends on PKA activity and protein synthesis during the early post-training period.     

Photodynamic therapy of skin cancer: controlled drug delivery of 5-ALA and its esters

Photodynamic therapy (PDT) is a tool for the treatment of certain cancerous and pre-cancerous conditions in dermatology. 5-Aminolevulinic acid (5-ALA) and simple derivatives thereof are the principal compounds used for this purpose. For optimal efficacy, the drug must be released at an appropriate rate from the formulation and penetrate the skin, ideally to reach the target tissue at a sufficiently high concentration. Because ALA is a polar, zwitterionic compound, its formulation in conventional topical vehicles, and its inherently poor skin permeability, poses important challenges for the pharmaceutical scientist. The synthesis of more lipophilic (e.g. ester) prodrugs of ALA resolves, in part, these issues but then demands that questions, related to biotransformation back to the parent 5-ALA and to stability, be addressed. The objective of this review, therefore, is to evaluate the state-of-the-art and identify those areas in which additional research is necessary.     

Azasterols as inhibitors of sterol 24-methyltransferase in Leishmania species and Trypanosoma cruzi

This paper describes the synthesis of some novel azasterols based on (20R,22xi)-5alpha-pregnan-20-(piperidin-2-yl)-3beta,20-diol. These compounds are potential inhibitors of the enzyme sterol 24-methyltransferase (24-SMT), which is a vital enzyme in the biosynthesis of ergosterol and related 24-alkyl sterols. Structure-activity studies were undertaken to understand the important features for activity against the enzyme, with the aim of increasing activity and selectivity. The compounds were evaluated for inhibition of recombinant Leishmania major 24-SMT and the effect of compounds on sterol composition and parasite proliferation. Essentially, compounds which showed good activity against the recombinant enzyme had a significant effect on the sterol composition and growth of parasites. The activity of compounds was found to be related to the basicity and stereochemical location of the nitrogen. Also, presence of an unprotected 3beta-OH seemed to be important for activity. However, some azasterols which were not good inhibitors of 24-SMT also showed antiproliferative activity, suggesting that there may be other modes of actions of these compounds.     

Alemtuzumab (Campath-1H) combined with tacrolimus in intestinal and multivisceral transplantation

BACKGROUND: We combined alemtuzumab (Campath-1H, Berlex Laboratories, Montville, NJ) and tacrolimus (Tac) immunosuppression for intestinal and multivisceral transplantation. MATERIALS AND METHODS: A total of 21 adult patients received 24 grafts: 14 intestinal, nine multivisceral, and one liver-intestinal graft. Alemtuzumab was administered perioperatively in four doses with low-dose Tac (levels 10-15 ng/dL) and no maintenance steroids. Tac was substituted with sirolimus in case of Tac-related complications. Suspected or mild rejections were treated with steroids. Moderate rejections were treated with steroids or OKT3. Severe rejections were treated with OKT3. RESULTS: Of the 16 patients that were followed up for an average of 9 months, 12 are alive with functioning grafts. Two patients experienced severe rejection, three experienced moderate rejection episodes, and seven experienced mild acute rejection episodes. Four patients never developed acute rejection. Infectious complications included a cytomegalovirus enteritis and four fungal infections (related to central venous access). CONCLUSIONS: The combination of alemtuzumab and Tac therapy without steroid use seems to efficiently prevent acute rejection in a significant number of patients without causing frequent opportunistic infections.