Disseminated Fusarium oxysporum neurospinal infection

We report a case of disseminated meningospondylodiscitis in an elderly diabetic patient caused by Fusarium oxysporum. As the clinical presentation was nonspecific, the diagnosis of the condition could only be arrived at after laboratory and imaging studies. The diagnosis of the condition requires a high index of suspicion. Patient underwent thorough surgical debridement along with a short course of variconazole and remained asymptomatic after 36 months of diagnosis. Fusarium is a large genus of filamentous fungi widely distributed in soil and in association with plants. It is known to cause local infections (nail, cornea) in healthy humans and disseminated infection only in the immunocompromised.     

An overview of new antitubercular drugs,drug candidates,and their targets

The causative agent of tuberculosis (TB), Mycobacterium tuberculosis and more recently totally drug-resistant strains of M. tuberculosis, display unique mechanisms to survive in the host. A four-drug treatment regimen was introduced 40 years ago but the emergence of multidrug-resistance and more recently TDR necessitates the identification of new targets and drugs for the cure of M. tuberculosis infection. The current efforts in the drug development process are insufficient to completely eradicate the TB epidemic. For almost five decades the TB drug development process remained stagnant. The last 10 years have made sudden progress giving some new and highly promising drugs including bedaquiline, delamanid, and pretomanid. Many of the candidates are repurposed compounds, which were developed to treat other infections but later, exhibited anti-TB properties also. Each class of drug has a specific target and a definite mode of action. These targets are either involved in cell wall biosynthesis, protein synthesis, DNA/RNA synthesis, or metabolism. This review discusses recent progress in the discovery of newly developed and Food and Drug Administration approved drugs as well as repurposed drugs, their targets, mode of action, drug-target interactions, and their structure-activity relationship.     

The use of microwave energy to cure denture acrylic resins

Experiments have been carried out on the curing of poly(methyl methacrylate) denture base material in a microwave oven, using conventional dental flasks and flask clamps. It has been shown that it is important (a) to maintain sufficient pressure on the materials, (b) to avoid gaseous porosity by not heating too rapidly initially, and (c) to ensure that all metal is protected from exposure to microwaves. When the appropriate conditions of polymerisation were used, microwave-cured samples had satisfactory physical and mechanical properties according to American Dental Association specification number 12.     

Current concepts in intervertebral disc restoration

A current focus of treatment for degenerative disk disease is the restoration of the intervertebral disk. This article summarizes the structure and function of the intervertebral disk, the pathogenesis of its degeneration, and the clinical relevance of degenerative disk disease. Current literature relating to intervertebral disk replacement and regeneration is reviewed.     

Transient iatrogenic immunodeficiency‐related B‐cell lymphoproliferative disorder of the skin in a patient with mycosis fungoides/Sézary syndrome

Immunodeficiency‐related lymphoproliferative disorders (IR‐LPD) may occur in the setting of immunosuppressive therapy with methotrexate and TNF‐α antagonists. As far as we are aware, this is the first report of an Epstein‐Barr virus‐associated B‐cell lymphoproliferative disorder, secondary to methotrexate therapy in a patient with mycosis fungoides/Sézary syndrome. Curry JL, Prieto VG, Jones DM, Vega F, Duvic M, Diwan AH. Transient iatrogenic immunodeficiency‐related B‐cell lymphoproliferative disorder of the skin in a patient with mycosis fungoides/Sézary syndrome.     

Effects of different stimulation parameters on the antidepressant-like response of medial prefrontal cortex deep brain stimulation in rats

Subcallosal cingulate gyrus (SCG) deep brain stimulation (DBS) is currently being investigated as a treatment for major depression. Despite the encouraging findings of the initial clinical series, several questions remain unanswered, including the most effective stimulation parameters (i.e., current intensity and frequency) and whether unilateral stimulation is also beneficial. We have recently found that some of the effects of SCG DBS could be modeled by stimulating the ventromedial prefrontal cortex (vmPFC) of rats undergoing the forced swim test (FST). Here we investigate whether changes in a number of DBS parameters, including electrode placement, influence outcome in this paradigm. Overall, we found that the antidepressant-like effects of DBS varied as a function of stimulation settings and target. The strongest response was observed with a current intensity of 200 μA, followed by 100 μA, and 300 μA. In contrast, 400 μA produced no effect. Using 200 μA, a frequency of 130 Hz was more effective than 20 Hz. An intriguing finding was that left unilateral stimulation was as effective as bilateral DBS. When different targets within the vmPFC were considered, a significant antidepressant-like response was observed after PL DBS, whereas IL stimulation was associated with a non-significant reduction in immobility scores. In summary, vmPFC DBS at high frequency and moderate intensity led to a maximal response in the FST.     

25. Ischemic Pain in the Extremities and Raynaud’s Phenomenon

Two important groups of disorders result from an insufficient blood supply to the extremities: critical vascular disease and the Raynaud’s phenomenon. The latter can be subdivided into a primary and a secondary type. Critical ischemic disease is often caused by arteriosclerosis due to hypertension or diabetes. Primary Raynaud’s is idiopathic and will be diagnosed as such if underlying systemic pathology has been excluded. Secondary Raynaud’s is often a manifestation of a systemic disease. It is essential to try to establish a diagnosis as soon as possible in order to influence the evolution of the disease. A sympathetic nerve block can be considered in patients with critical ischemic vascular disease after extensive conservative treatment, preferably in the context of a study (2B±). If this has insufficient effect, spinal cord stimulation can be considered in a selected patient group (2B±). In view of the degree of invasiveness and the costs involved, this treatment should preferably be applied in the context of a study and with the use of transcutaneous pO₂ measurements. In case of primary Raynaud’s, life style changes are the first step. Sympathectomy can be considered as a treatment of Raynaud’s phenomenon (2C+), but only after multidisciplinary evaluation of the patient and in close consultation with the patient’s rheumatologist, vascular surgeon or internist.     

Enhancement of thyroid and hepatocarcinogenesis by 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene in rats at doses that cause maximal induction of CYP2B

To investigate the promoting effects of 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene(TCPOBOP) on liver and thyroid carcinogenesis of rats at dosesthat cause maximal induction of hepatic CYP2B, 5-week-old maleF344 rats were given either a single i.p. dose of 75 mg N-nitrosodiethylamine(NDEA)/kg body wt in saline or saline alone. After 2 weeks therats were fed control diet or a diet containing 330 or 1000p.p.m. TCPOBOP or 500 p.p.m. phenobarbital (PB; a positive controlgroup). A total of four sequential sacrifices (9, 30, 52 and79 weeks of age) was performed. At 30 weeks the mean volume(mm³) of hepatocellular foci in NDEA-initiated rats exposedto either dose of TCPOBOP or to PB was significantly increasedas compared with rats exposed to NDEA followed by control diet(P < 0.05). In addition, the volume percentage of liver occupiedby foci was significantly greater in NDEA-initiated/1000 p.p.m.TCPOBOP-promoted rats as compared with rats exposed to NDEAalone (P < 0.05, n = 6). At 52 weeks of age the incidences(and multiplicities, in units of tumors per tumor-bearing rat)of hepatocellular adenomas were 0, 83 (2.6 ± 1.3), 100(3.4 ± 2.1) or 67% (2.5 ± 1.9) in rats exposedto NEDA alone or NDEA followed by 330 or 1000 p.p.m. TCPOBOPor 500 p.p.m. PB respectively (n = 12). Hepatocellular carcinomaswere found only in rats given 1000 p.p.m. TCPOBOP (17% incidence)or PB (8% incidence) following NDEA initiation. The incidencesof thyroid follicular cell adenomas were 0, 17, 33 or 8% inrats exposed to NDEA alone or NDEA followed by 330 or 1000 p.p.m.TCPOBOP or 500 p.p.m. PB respectively. Between 53 and 79 weeksof age 38% of rats treated with NDEA alone developed multiple(1.5 ± 0.8) hepatocellular adenomas. This incidence wasenhanced to 100% in rats exposed to NDEA followed by either330 or 1000 p.p.m. TCPOBOP. Multiplicities of hepatocellularadenomas were also increased significantly (10.5 ± 3.9,10.4 ± 7.0 and 10.1 ± 6.7 respectively) in ratspromoted with 330 or 1000 p.p.m. TCPOBOP or 500 p.p.m. PB. Noneof the rats exposed to NDEA alone developed hepatocellular carcinomas,while multiple hepatocellular carcinomas occurred in 38% ofthe rats exposed to 330 p.p.m. and 78% of the rats given 1000p.p.m. TCPOBOP following NDEA initiation. Thyroid follicularcell tumors occurred at 79 weeks in more than 40 and 50% incidencesin rats exposed to NDEA followed by 330 or 1000 p.p.m. TCPOBOPrespectively. Also, a significant decrease in serum levels oftriiodothyronine and thyroxine were observed in non-initiated79-week-old rats fed 1000 p.p.m. TCPOBOP, compared with age-matcheduntreated controls (n = 6). Increases in hepatic CYPC2B-mediatedbenzyloxy-resorufin O-dealkylase activity detected in rats exposedto 330 and 1000 p.p.m. TCPOBOP for 2 or 23 weeks were similarin magnitude to those caused by 500 p.p.m. PB. Thus TCPOBOPat maximal CYP2B induction doses exhibits a strong promotingactivity for both liver and thyroid of rats.     

Critical windows of exposure for children's health: cancer in human epidemiological studies and neoplasms in experimental animal models

In humans, cancer may be caused by genetics and environmental exposures; however, in the majority of instances the identification of the critical time window of exposure is problematic. The evidence for exposures occurring during the preconceptional period that have an association with childhood or adulthood cancers is equivocal. Agents definitely related to cancer in children, and adulthood if exposure occurs in utero, include: maternal exposure to ionizing radiation during pregnancy and childhood leukemia and certain other cancers, and maternal use of diethylstilbestrol during pregnancy and clear-cell adenocarcinoma of the vagina of their daughters. The list of environmental exposures that occur during the perinatal/postnatal period with potential to increase the risk of cancer is lengthening, but evidence available to date is inconsistent and inconclusive. In animal models, preconceptional carcinogenesis has been demonstrated for a variety of types of radiation and chemicals, with demonstrated sensitivity for all stages from fetal gonocytes to postmeiotic germ cells. Transplacental and neonatal carcinogenesis show marked ontogenetic stage specificity in some cases. Mechanistic factors include the number of cells at risk, the rate of cell division, the development of differentiated characteristics including the ability to activate and detoxify carcinogens, the presence of stem cells, and possibly others. Usefulness for human risk estimation would be strengthened by the study of these factors in more than one species, and by a focus on specific human risk issues.