Group B and F Beta Streptococcus Necrotizing Infection-Surgical Challenges with a Deep Central Plantar Space Abscess A Diabetic Limb Salvage Case Report.

We present the case of a 66-year-old, type II diabetic male with a deep wound to the plantar-lateral aspect of his right hallux. On examination, the central plantar compartment of his right foot was moderately erythematous and tender on palpation. After obtaining a deep wound culture, treatment was complicated by a progression of a group B and F beta streptococcus, necrotizing infection.

Group B and F Beta Streptococcus Necrotizing Infection-Surgical Challenges with a Deep Central Plantar Space Abscess: A Diabetic Limb Salvage Case Report.

We present the case of a 66-year-old, type II diabetic male with a deep wound to the plantar-lateral aspect of his right hallux. On examination, the central plantar compartment of his right foot was moderately erythematous and tender on palpation. After obtaining a deep wound culture, treatment was complicated by a progression of a group B and F beta streptococcus, necrotizing infection.

Open reduction-internal fixation of a navicular body fracture with dorsal displacement of the first and second cuneiforms: a case report.

Body fractures of the tarsal navicular are relatively uncommon. To date, there is little literature discussing a navicular body fracture with dorsal subluxation of the first and second cuneiforms over the navicular. This case study presents a 30-year-old patient with this injury.

Angiokeratoma presenting as a melanoma: a case report.

Angiokeratomas are benign skin lesions that can resemble melanomas or verrucae. Although morbidity from these lesions is rare, treatment for angiokeratomas typically consists of simple surgical excision. We aim to describe a case of a painful angiokeratoma that presented with the appearance of melanoma.

Pilomatrixoma: an infrequently encountered lesion on the lower extremity.

We discuss the clinical presentation and treatment of pilomatrixoma as it occurs in the lower extremity. Although pilomatrixoma is far more common on the head, neck, and upper extremity, it can be found on the lower extremity. Treatment is aimed primarily at excision if the lesion is symptomatic or suspicious for malignancy.

A mechanically powered negative pressure device used in conjunction with a bioengineered cell-based product for the treatment of pyoderma gangrenosum: a case report .

Pyoderma gangrenosum (PG), an uncommon inflammatory and ulcerative skin disease, typically is treated medically with a combination of immunosuppression and local wound care, but evidence to guide care is limited. PG wounds can be difficult to heal. A 76-year-old male patient presented with a history of rheumatoid arthritis and recalcitrant PG.

A case of a sural neuroma as a cause of lateral ankle pain.

This article reviews the diagnosis, pathology, and treatment of a lateral ankle (sural) neuroma. Though there have been vague references to neuroma of the sural nerve, no specific case report has been presented. It is felt that mechanical and biomechanical factors may contribute to the formation of this type of painful mass which warrants further discussion as an additional etiology of lateral ankle pain.

HIV neuropathy induced Charcot neuroarthropathy: a case discussion.

Charcot neuroarthropathy is a devastating joint condition that affects persons with neuropathy. With HIV/AIDS treatments prolonging the lives of these persons, it is likely that long-term sequelae of the disease will become more evident in the near future. Patients with this disease frequently develop peripheral neuropathy.

Synthesis and pharmacology of 1-alkyl-3-(1-naphthoyl)indoles: steric and electronic effects of 4- and 8-halogenated naphthoyl substituents.

To develop SAR at both the cannabinoid CB(1) and CB(2) receptors for 3-(1-naphthoyl)indoles bearing moderately electron withdrawing substituents at C-4 of the naphthoyl moiety, 1-propyl and 1-pentyl-3-(4-fluoro, chloro, bromo and iodo-1-naphthoyl) derivatives were prepared. To study the steric and electronic effects of substituents at the 8-position of the naphthoyl group, the 3-(4-chloro, bromo and iodo-1-naphthoyl)indoles were also synthesized. The affinities of both groups of compounds for the CB(1) and CB(2) receptors were determined and several of them were evaluated in vivo in the mouse.

1-Pentyl-3-phenylacetylindoles and JWH-018 share in vivo cannabinoid profiles in mice.

Background: Smoking of synthetic cannabinoid-enhanced "herbal incense" is an emerging substance abuse problem. The indole-derived cannabinoids identified in these products were originally developed as research tools and are structurally distinct from cannabinoids in the cannabis plant. Although abused by humans, most published research on this class of compounds has been performed in vitro.

Structural and pharmacological analysis of O-2050, a putative neutral cannabinoid CB(1) receptor antagonist.

Rimonabant, the prototypic antagonist of cannabinoid CB(1) receptors, has been reported to have inverse agonist properties at higher concentrations, which may complicate its use as a tool for mechanistic evaluation of cannabinoid pharmacology. Consequently, recent synthesis efforts have concentrated on discovery of a neutral antagonist using a variety of structural templates. The purpose of this study was to evaluate the pharmacological properties of the putative neutral cannabinoid CB(1) receptor antagonist O-2050, a sulfonamide side chain analog of Δ(8)-tetrahydrocannabinol.

1-Bromo-3-(1',1'-dimethylalkyl)-1-deoxy-Δ(8)-tetrahydrocannabinols: New selective ligands for the cannabinoid CB(2) receptor.

Δ(8)-Tetrahydrocannabinol (26), 3-(1',1'-dimethylbutyl)- (12), 3-(1',1'-dimethylpentyl)- (13), 3-(1',1'-dimethylhexyl)- (14) and 3-(1',1'-dimethylheptyl)-Δ(8)-tetrahydrocannabinol (15) have been converted into the corresponding 1-bromo-1-deoxy-Δ(8)-tetrahydrocannabinols (25, 8-11). This was accomplished using a protocol developed in our laboratory in which the trifluoromethanesulfonate of a phenol undergoes palladium mediated coupling with pinacolborane. Reaction of this dioxaborolane with aqueous-methanolic copper(II) bromide provides the aryl bromide.

Synthesis and pharmacology of 1-methoxy analogs of CP-47,497.

Three 1-methoxy analogs of CP-47,497 (7, 8, and 19) have been synthesized and their affinities for the cannabinoid CB(1) and CB(2) receptors have been determined. Although these compounds exhibit selectivity for the CB(2) receptor none have significant affinity for either receptor. Modeling and receptor docking studies were carried out, which provide a rationalization for the weak affinities of these compounds for either receptor.

Synthesis, nicotinic acetylcholine receptor binding, and antinociceptive properties of 3'-(substituted phenyl)epibatidine analogues. Nicotinic partial agonists.

In 1992, John Daly et al. reported the isolation and structure determination of epibatidine. Epibatidine's unique structure and its potent nicotinic agonist activity have had a tremendous impact on nicotine receptor research.

Characterization of pharmacological and behavioral differences to nicotine in C57Bl/6 and DBA/2 mice.

Approximately 50-70% of the risk for developing nicotine dependence is attributed to genetics; therefore, it is of great significance to characterize the genetic mechanisms involved in nicotine reinforcement and dependence in hopes of generating better smoking cessation therapies. The overall goal of these studies was to characterize behavioral and pharmacological responses to nicotine in C57Bl/6 (B6) and DBA/2 (D2) mice, two inbred strains commonly used for genetic studies on behavioral traits. B6 and D2 mice where subjected to a battery of behavioral tests to measure nicotine's acute effects, calcium-mediated antinociceptive responses, tolerance to chronic treatment with osmotic mini pumps, and following three days of nicotine withdrawal.

Modulation of motor and sensory pathways of the peristaltic reflex by cannabinoids.

Cannabinoids have long been known to be potent inhibitors of intestinal and colonic propulsion. This effect has generally been attributed to their ability to prejunctionally inhibit release of acetylcholine from excitatory motor neurons that mediate, in part, the ascending contraction phase of the peristaltic reflex. In the present study we examined the effect of cannabinoids on the other transmitters known to participate in the peristaltic reflex using a three-compartment preparation of rat colon that allows separation of ascending contraction, descending relaxation, and the sensory components of the reflex.

Prolonged exposure to WIN55,212-2 causes downregulation of the CB1 receptor and the development of tolerance to its anticonvulsant effects in the hippocampal neuronal culture model of acquired epilepsy.

Cannabinoids have been shown to cause CB1-receptor-dependent anticonvulsant activity in both in vivo and in vitro models of status epilepticus (SE) and acquired epilepsy (AE). It has been further demonstrated in these models that the endocannabinoid system functions in a tonic manner to suppress seizure discharges through a CB1-receptor-dependent pathway. Although acute cannabinoid treatment has anticonvulsant activity, little is known concerning the effects of prolonged exposure to CB1 agonists and development of tolerance on the epileptic phenotype.

Discriminative stimulus properties of delta9-tetrahydrocannabinol (THC) in C57Bl/6J mice.

Primarily, rats have served as subjects in Delta(9)-tetrahydrocannabinol's (THC) discrimination studies although other species such as monkeys and pigeons have been used. While the introduction of the knockout and transgenic mice has vastly stimulated the study of the discriminative stimulus effects of drugs there is only a single published report of mice trained to discriminate THC. Thus, this study extended those results by providing a systematic replication that THC serves as an effective discriminative stimulus in mice and by further investigating the mechanisms of action involved in the THC discrimination model in the mouse.

Temporal characterization of changes in hippocampal cannabinoid CB(1) receptor expression following pilocarpine-induced status epilepticus.

Several reports have focused on the involvement of the endocannabinoid system in hyperexcitability, particularly in seizure and epilepsy models. Our laboratory recently characterized a novel plasticity change of the cannabinoid type 1 (CB(1)) receptor in hippocampi of epileptic rats following pilocarpine-induced status epilepticus (SE). This long-term redistribution included selective layer-specific changes in CB(1) receptor expression within distinct hippocampal subregions.

Modulation of cannabinoid receptor activation as a neuroprotective strategy for EAE and stroke.

Recognition of the importance of the endocannabinoid system in both homeostasis and pathologic responses raised interest recently in the development of therapeutic agents based on this system. The CB(2) receptor, a component of the endocannabinoid system, has significant influence on immune function and inflammatory responses. Inflammatory responses are major contributors to central nervous system (CNS) injury in a variety of diseases.

3'-Fluoro substitution in the pyridine ring of epibatidine improves selectivity and efficacy for alpha4beta2 versus alpha3beta4 nAChRs.

The analog of epibatidine having a fluoro substituent at the 3' position of the pyridine ring has been recently developed and shown to possess binding affinity in the pM range to alpha4beta2 nAChRs and in the nM range to alpha7 nAChRs and to exhibit potent agonist activity in nicotine-induced analgesia tests. Here we used patch-clamp technique in a whole-cell configuration to compare functional activity of 3'-fluoroepibatidine to that of epibatidine by itself on recombinant alpha4beta2, alpha7 and alpha3beta4 neuronal nAChRs. The agonist effect of (+/-)-epibatidine was partial and yielded comparable EC50s of 0.

The cannabinoid delta-9-tetrahydrocannabinol mediates inhibition of macrophage chemotaxis to RANTES/CCL5: linkage to the CB2 receptor.

The chemotactic response of murine peritoneal macrophages to RANTES/CCL5 was inhibited significantly following pretreatment with delta-9-tetrahydrocannabinol (THC), the major psychoactive component in marijuana. Significant inhibition of this chemokine directed migratory response was obtained also when the full cannabinoid agonist CP55940 was used. The CB2 receptor-selective ligand O-2137 exerted a robust inhibition of chemotaxis while the CB1 receptor-selective ligand ACEA had a minimal effect.

Divergent effects of cannabidiol on the discriminative stimulus and place conditioning effects of Delta(9)-tetrahydrocannabinol.

Cannabis sativa (marijuana plant) contains myriad cannabinoid compounds; yet, investigative attention has focused almost exclusively on Delta(9)-tetrahydrocannabinol (THC), its primary psychoactive substituent. Interest in modulation of THC's effects by these other cannabinoids (e.g.

WIN55,212-2-mediated inhibition of HIV-1 expression in microglial cells: involvement of cannabinoid receptors.

Cannabinoid receptors CB(1) and CB(2) are primarily expressed in cells of the nervous and immune systems, respectively. Recently, the synthetic CB(1)/CB(2) agonist WIN55,212-2 was found to suppress replication of HIV-1 in microglial cell cultures. The present study was undertaken to test the hypothesis that WIN55,212-2's antiviral effect is mediated via CB(2) receptors.

Synthesis and nicotinic acetylcholine receptor binding properties of bridged and fused ring analogues of epibatidine.

Epibatidine analogues 3- 5, possessing the pyridine ring fused to the 2,3 position of the 7-azabicyclo[2.2.1]heptane ring, and analogue 8a, possessing a benzene ring fused to the 5,6 position, were synthesized by procedures involving key steps of trapping 2,3-pyridyne, 3,4-pyridyne, and benzyne with tert-butyl 1 H-pyrrole-1-carboxylate.