Orthogonal solid-phase synthesis of a monobiotinylated analog of Neuropeptide Y

Analogs of Neuropeptide Y (NPY) were synthesized with conventional Boc/benzyl protective group strategy. Instead of Asn⁷ in the native scquence, Boc-Lys(Alloc)-OH was incorporated. At the end of the synthesis the Alloc group was selectively removed by palladium-catalyzed hydrostannolysis and biotin coupled to the e-amino group of Lys⁷. After cleavage and characterization with plasma desorption mass spectrometry the N^e-7-biotinyl-[Lys⁷]-NPY and the nonbiotinylated analog [Lys⁷]-NPY were investigated as ligands to the NPY receptor from rat cerebral cortex. Both analogs were found to be high affinity ligands to the NPY receptor and bound with essentially the same affinity as unmodified NPY.     

Protective effect of pentoxifylline plus thalidomide against septic shock in mice

Mortality caused by septic shock in experimental animals is reduced by thalidomide, an inhibitor of tumour necrosis factor alpha. Another drug that could act on the pathophysiological mechanisms of septic shock is pentoxifylline, an inhibitor of platelet aggregation that increases the flexibility of the erythrocyte membrane and has fibrinolytic activity. We studied the effect of pentoxifylline alone and combined with thalidomide in septic shock; 97 NIH mice were injected with lipopolysaccharides of Salmonella abortus equi and D galactosamine. Animals were separated in 4 groups; group A (n = 20) was used as control, group B (n = 15) received thalidomide 50 mg/kg, group C (n = 20) received pentoxifylline 40 mg/kg, and group D (n = 15) received thalidomide plus pentoxifylline. Mortality was recorded every hour. Additionally, 5 animals from each group were sacrificed 8 h after the induction of septic shock for histological analysis of heart, lung, brain, kidney, small intestine, adrenal glands and liver. Microscopic findings were rated as absent, mild, moderate and severe damage. In control animals histological analysis showed intense haemorrhage and necrosis in all organs studied. When compared with controls, treatment with pentoxifylline plus thalidomide reduced mortality (P < 0.03). The tissue damage was less severe in animals from the groups that received pentoxifylline or pentoxifylline plus thalidomide (P < 0.05). Pentoxifylline seems to potentiate the beneficial effects of thalidomide, reducing mortality and attenuating the pathological changes produced by septic shock.     

Modulation of T-cell responsiveness during Trypanosoma cruzi infection: analysis in different lymphoid compartments

Spleen and lymph node cells of Trypanosoma cruzi-infected mice were studied for mitogen-induced responsiveness in terms of proliferation and lymphokine production (IL-2, IFN-gamma). Splenocyte (SP) as well as lymph node cell (LN) proliferation and IL-2 production were depressed during the acute phase of the infection. Proliferative capacity of LN cells recovered completely and that of SP partially during the chronic phase. In contrast to these suppressive effects, the mitogen-induced IFN-gamma response was enhanced. In vitro co-incubation of normal SP or LN cells with trypomastigotes resulted in a reduced mitogen-induced cell proliferation and IL-2 secretion, similar to those seen with cells taken from infected mice. In contrast, trypomastigotes exerted a stimulatory activity on the mitogen-induced IFN-gamma response of both SP and LN cells. Addition of lymph node cells from T. cruzi-infected mice (LN-I) to lymph node cells of control mice (LN-C) suppressed strongly the mitogen-induced responsiveness of such cocultures. A marginal level of suppression was recorded in cocultures of spleen cells from infected mice (SP-I) and control spleen cells (SP-C). The potent suppressive cells within LN-I populations were identified as macrophage-like and such cells were absent in SP-C and peritoneal exudate cells from T. cruzi infected animals.     

EFFECT OF ACUTE AND CHRONIC NEUROLEPTIC THERAPY ON SERUM PROLACTIN LEVELS IN MEN AND WOMEN OF DIFFERENT AGE GROUPS

A single fasting level of serum prolactin was measured in each of sixty control subjects and eighty-three psychiatric patients of both sexes who had been on neuroleptic therapy for 2-4 weeks (acute treatment) or at least 5 years (chronic treatment) and who were aged either 17-45 or 48-85 years. All groups of patients had significantly higher mean prolactin levels than controls. Gender, age group of women, and exposure to acute or chronic treatment were significant variables determining the magnitude of neuroleptic-induced elevation of prolactin. In some of the groups, dose, duration of chronic therapy, and concomitant administration of anticholinergic drugs also influenced prolactin levels. Whereas all acutely treated women had prolactin values above the control range, one out of twelve (8.3%) of the women aged 17-45 years and six out of fourteen (42.9%) of the women aged 48-85 years who were under chronic treatment had normal values. Normal prolactin levels were also found in five out of sixteen (31.2%) of the acutely treated and nine out of twenty-four (37.5%) of the chronically treated men aged 17-85 years.     

Longitudinal tooth fractures: findings that contribute to complex endodontic diagnoses

The purpose of this review is to describe and discuss the diagnostic and treatment challenges related to tooth fractures primarily in the vertical plane, that is, the long axis of the crown and/or root. This includes when and how to identify and determine the extent of the fracture, when a coronal restoration should be placed, when root canal treatment is needed, and when a tooth or root should be extracted based on the location and extent of the fracture. The term ‘longitudinal fractures’ is used because they usually represent vertical extensions of fractures over distance and time. These fractures often present problems with diagnosis and treatment, but should be considered as findings only. They are not to be considered as pulpal or periapical diagnoses, but as pathways for bacteria that may induce pulpal and/or periapical inflammation or disease. Longitudinal fractures are divided into five definitive classifications, generally from least to most severe: (1) craze lines; (2) fractured cusp; (3) cracked tooth; (4) split tooth; and (5) vertical root fracture. These differ but have frequently been confused or combined in clinical articles, creating misunderstanding and resulting in incorrect diagnosis and inappropriate treatment. These classifications have been devised to provide global definitions that researchers and clinicians can use to eliminate this confusion. This review is subdivided into these five classifications as to incidence, pathogenesis, clinical features, etiologies, diagnosis, treatment, prognosis, and prevention.