Evidence for the treatment of moderate depression: a systematic review.

OBJECTIVES: This study aims to investigate existing evidence for the effectiveness of psychological treatments and/or antidepressant medication as a treatment for those diagnosed with moderate levels of depression. METHODS: A PRISMA systematic review of articles using electronic research databases (2000-2014) was conducted to identify studies investigating the effectiveness of psychotherapy and/or medication as a treatment for people with moderate levels of depression. Search terms included moderate depression, psychotherapy and/or medication, depressive disorders, antidepressants, psychotherapy, mental health services, and randomized-controlled trial (RCT). The included studies were then assessed, extracted, and synthesised. RESULTS: A total of 14 studies met the inclusion criteria (11 RCTs and three additional studies) for this review. The findings of the systematic review indicate that there is limited evidence available specific to the treatment of moderate depression and that this research seems to suggest that psychotherapy or combined treatment has a beneficial effect. CONCLUSIONS: Given that depression is one of the biggest challenges the world faces at present, further research is required to examine the effectiveness of treatment for different levels of depression severity.

Investigation of the multifaceted iron acquisition strategies of Burkholderia cenocepacia.

Burkholderia cenocepacia is a bacterial pathogen which causes severe respiratory infections in cystic fibrosis (CF). These studies were aimed at gaining an insight into the iron acquisition strategies of B. cenocepacia. In iron restricted conditions, genes associated with the synthesis and utilisation of ornibactin (pvdA, orbA, orb F) were significantly upregulated compared to the expression of pyochelin associated genes (pchD, fptA). In the absence of alternative iron sources, B. cenocepacia J2315 and 715j utilised ferritin and haemin, but not transferrin or lactoferrin for growth. Significantly, mutants unable to produce ornibactin, (715j-orbI) or ornibactin and pyochelin, (715j-pobA), utilised haemin and ferritin more efficiently than the wild-type. Moreover, both mutants were also able to utilise lactoferrin for growth (P ≤ 0.01) and additionally 715j-pobA utilised transferrin (P ≤ 0.01), potentially facilitating adaptation to the host environment. Furthermore, B. cenocepacia increased ornibactin gene expression in response to pyoverdine from Pseudomonas aeruginosa (P ≤ 0.01), demonstrating the capacity to compete for iron in co-colonised niches. Pyoverdine also significantly diminished the growth of B. cenocepacia (P < 0.001) which was related to its iron chelating activity. In a study of three B. cenocepacia sequential clonal isolates obtained from a CF patient over a 3.5 year period, ornibactin upregulation in response to pyoverdine was less pronounced in the last isolate compared to the earlier isolates, as was growth in the presence of haemin and ferritin, indicating alternative iron acquisition mechanism(s) may dominate as chronic infection progresses. These data demonstrate the multifaceted iron acquisition strategies of B. cenocepacia and their capacity to be differentially activated in the presence of P. aeruginosa and during chronic infection.

Alpha and gamma herpesvirus detection in two herds of farmed red deer (Cervus elaphus) in New Zealand.

CASE HISTORY: In September 2004 two hinds on Farm 1 were observed with epiphora and keratoconjunctivitis, and corneal scarring. A low pregnancy rate in some hinds had been recorded that year. In the same year six yearling deer were observed on Farm 2 with keratitis, uveitis and corneal scarring. CLINICAL AND PATHOLOGICAL FINDINGS: On Farm 1, conjunctival swabs and blood samples were collected from the hinds with ocular lesions, and from 24 other hinds. The two affected hinds were immunosuppressed with dexamethasone for 7 days. Conjunctival, nasal and vaginal swabs were collected daily before euthanasia and necropsy on the eighth day. Subsequently, another five non-pregnant hinds were similarly immunosuppressed and necropsied, and the reproductive tracts of 20 non-pregnant hinds were collected following slaughter. Semen samples were collected from four stags implicated with reproductive failure. On Farm 2, conjunctival swabs were collected from six hinds with ocular lesions and from 14 unaffected deer. Viral culture, consensus primer PCR and sequencing for specific herpesviruses was carried out on conjunctival swabs, buffy coat from blood samples, semen and reproductive tracts. Necropsy samples were also examined using gross pathology and histopathology. On Farm 1, a type 2 rhadinovirus (CvRhV) was detected in the conjunctiva of one hind with keratoconjunctivitis using PCR. Following immunosuppression, gross vesicular and histological vaginal lesions typical of infection with alphaherpesvirus were observed in samples of vaginal tissue from the same hind. Buffy coat, vaginal and lumbar spinal nervous tissues were also positive for cervid herpesvirus 1 (CvHV-1) using PCR. Herpesviruses were not detected in reproductive tracts, ocular or semen samples of the other deer. CvRhV was detected in buffy coats from four other hinds and in a conjunctival swab from one hind, all without ocular lesions, using PCR. On Farm 2, conjunctival swabs from two deer with keratitis were culture positive for CvHV-1. Two culture-negative conjunctival samples from deer without ocular lesions were positive for CvHV-1 by PCR. In two other affected animals, presence of CvRhV was confirmed by PCR and sequencing. DIAGNOSIS: Infection with CvHV-1 associated with keratitis and vulvovaginitis, and CvRhV infection in deer with and without ocular lesions. CLINICAL RELEVANCE: CvHV-1 is a likely cause of keratoconjunctivitis and possibly reproductive tract pathology in deer. Investigation of ocular lesions and reproductive failure in farmed deer should include CvRhV and CvHV-1.

Efficacy of tropicamide, homatropine, cyclopentolate, atropine and hyoscine as mydriatics in Angora goats.

AIM: To document the efficacy of five commercially available mydriatics for their potential for diagnostic and therapeutic use in Angora goats. METHODS: Over 8 weeks, the mydriatic effects of 1% tropicamide, 2% homatropine, 1% cyclopentolate, 1% atropine and 0.25% hyoscine were evaluated. Given as block treatments, drugs were applied randomly to one eye of 10 Angora goats, and the contralateral eye served as a control. Vertical and horizontal pupil diameters were measured to document onset of effect, time to reach a difference of 5 mm in the vertical/horizontal pupil diameter between eyes, time to maximum pupillary dilation, and duration of mydriatic action. RESULTS: Onset of mydriasis for all drugs occurred within 15 minutes. Time to reach a difference of 5 mm in the vertical pupil diameter between eyes was shortest for 1% tropicamide and 0.25% hyoscine (0.5 h), then 2% homatropine and 1% atropine (0.75 h), and longest for 1% cyclopentolate (1.5 h). The maximum vertical pupillary dilation occurred earliest with 1% tropicamide and 1% atropine (2 h), followed by 0.25% hyoscine (3 h), 2% homatropine (4 h), and latest with 1% cyclopentolate (8 h). The duration of vertical dilation of the pupil was shortest with 1% tropicamide (6 h), then 2% homatropine (12 h), 1% cyclopentolate (12 h), 1% atropine (24 h), and longest for 0.25% hyoscine (96 h). The time to reach maximum horizontal dilation of the pupil in treated eyes was shortest with 1% cyclopentolate (1 h), followed by 1% tropicamide (1.5 h), 0.25% hyoscine (3 h), 2% homatropine (3.5 h), and 1% atropine (4 h). The duration of horizontal pupil dilation was shortest with 1% tropicamide (4.5 h), and longest with 0.25% hyoscine (48 h). CONCLUSION: All five mydriatics induced clinical dilation. Tropicamide (1%) had the shortest duration of effect, but gave incomplete dilation. Good dilation was achieved with 1% cyclopentolate and 2% homatropine, but took too long to reach maximum dilation for routine mydriasis. The largest vertical dilation of the pupil was achieved with 1% atropine and 0.25% hyoscine, but pupils remained dilated for more than 24 h. CLINICAL RELEVANCE: For routine mydriasis in goats, it is recommended that 1% tropicamide be used, though there may be incomplete dilation. For a longer duration of mydriasis, such as in the treatment of anterior uveitis, 1% atropine or 0.25% hyoscine would be the drugs of choice.

Therapeutic photobiomodulation for methanol-induced retinal toxicity.

Methanol intoxication produces toxic injury to the retina and optic nerve, resulting in blindness. The toxic metabolite in methanol intoxication is formic acid, a mitochondrial toxin known to inhibit the essential mitochondrial enzyme, cytochrome oxidase. Photobiomodulation by red to near-IR radiation has been demonstrated to enhance mitochondrial activity and promote cell survival in vitro by stimulation of cytochrome oxidase activity. The present studies were undertaken to test the hypothesis that exposure to monochromatic red radiation from light-emitting diode (LED) arrays would protect the retina against the toxic actions of methanol-derived formic acid in a rodent model of methanol toxicity. Using the electroretinogram as a sensitive indicator of retinal function, we demonstrated that three brief (2 min, 24 s) 670-nm LED treatments (4 J/cm(2)), delivered at 5, 25, and 50 h of methanol intoxication, attenuated the retinotoxic effects of methanol-derived formate. Our studies document a significant recovery of rod- and cone-mediated function in LED-treated, methanol-intoxicated rats. We further show that LED treatment protected the retina from the histopathologic changes induced by methanol-derived formate. These findings provide a link between the actions of monochromatic red to near-IR light on mitochondrial oxidative metabolism in vitro and retinoprotection in vivo. They also suggest that photobiomodulation may enhance recovery from retinal injury and other ocular diseases in which mitochondrial dysfunction is postulated to play a role.

Effect of NASA light-emitting diode irradiation on wound healing.

OBJECTIVE: The purpose of this study was to assess the effects of hyperbaric oxygen (HBO) and near-infrared light therapy on wound healing. BACKGROUND DATA: Light-emitting diodes (LED), originally developed for NASA plant growth experiments in space show promise for delivering light deep into tissues of the body to promote wound healing and human tissue growth. In this paper, we review and present our new data of LED treatment on cells grown in culture, on ischemic and diabetic wounds in rat models, and on acute and chronic wounds in humans. MATERIALS AND METHODS: In vitro and in vivo (animal and human) studies utilized a variety of LED wavelength, power intensity, and energy density parameters to begin to identify conditions for each biological tissue that are optimal for biostimulation. RESULTS: LED produced in vitro increases of cell growth of 140-200% in mouse-derived fibroblasts, rat-derived osteoblasts, and rat-derived skeletal muscle cells, and increases in growth of 155-171% of normal human epithelial cells. Wound size decreased up to 36% in conjunction with HBO in ischemic rat models. LED produced improvement of greater than 40% in musculoskeletal training injuries in Navy SEAL team members, and decreased wound healing time in crew members aboard a U.S. Naval submarine. LED produced a 47% reduction in pain of children suffering from oral mucositis. CONCLUSION: We believe that the use of NASA LED for light therapy alone, and in conjunction with hyperbaric oxygen, will greatly enhance the natural wound healing process, and more quickly return the patient to a preinjury/illness level of activity. This work is supported and managed through the NASA Marshall Space Flight Center-SBIR Program.

In vitro analysis of antiangiogenic activity of fungi isolated from clinical cases of equine keratomycosis.

OBJECTIVE: The goal of this project was to explore the possibility that fungal organisms produce metabolites that inhibit angiogenesis. Procedures Fungal cultures were obtained from cases of keratomycosis, grown in Sabouraud's dextrose broth, and sterile filtered for use in experiments. The Matrigel assay was used to screen the filtrate samples for antiangiogenic activity. Matrigel is a basement membrane matrix that supports the differentiation of human umbilical vein endothelial (HUVE) cells into a capillary-like network of tubules. HUVE cells were cultured using standard techniques and passaged at confluence, with all cells being used at passage 3-6. HUVE cells (40 000 cells) were pipetted into each well of a 24-well tissue-culture plate coated with Matrigel. An aliquot of fungal media filtrate was added to each well and the plates allowed to incubate for 18 h, at which time they were evaluated for tubule formation. RESULTS: Two fungal isolates showed inhibition of tubule formation. The addition of 100, 200 and 400 &mgr;L of the fungal media filtrate from the first isolate (Fusarium sp. 99A34574) produced a consistent and dose-dependent inhibition of tubule formation. The second isolate (Aspergillus sp. 271599) did not show inhibition of tubule formation with 100 or 200 &mgr;L added to the wells, however, it did show inhibition at 400 &mgr;L/well. The remaining three isolates did not cause inhibition at any concentration. CONCLUSIONS: Our findings suggest that certain fungal organisms produce metabolites that inhibit tubule formation in vitro, and that these metabolites may play a significant role in altering the host vascular response to fungal infections of the cornea.

Equine infectious keratitis.

Corneal ulcers are one of the most common ocular disease presentations in the horse. With the use of correct diagnostic techniques and selection of an appropriate treatment regimen, most cases result in a satisfactory outcome. The eye does not respond well to inflammation, and in complicated ulcers, this should be managed aggressively using systemic NSAIDs with a high priority assigned to removing the infectious agent. Care needs to be taken to avoid topical or systemic corticosteroid use for the treatment of equine ocular disease, however, unless the clinician is completely sure that the corneal disease is not caused by an infectious process. The use of combination corticosteroid-antibiotic ophthalmic preparations without an appropriate treatment rationale can result in doing more harm than good. It is important to have a treatment plan and to monitor the elected treatment regimen. The clinician should decide on some objective criteria at initiation of treatment so that any changes are made rationally. This approach should also include consideration of early referral of the eye's care to a veterinary ophthalmologist.

Preclinical evaluation of benzoporphyrin derivative combined with a light-emitting diode array for photodynamic therapy of brain tumors.

OBJECTIVE: The aim of this study was to investigate the second-generation photosensitizer benzoporphyrin derivative (BPD) and a novel light source applicator based on light-emitting diode (LED) technology for photodynamic therapy (PDT) of brain tumors. METHODS: We used a canine model to investigate normal brain stem toxicity. Twenty-one canines underwent posterior fossa craniectomies followed by PDT with BPD. These animals were compared to light only and BPD control. In addition, we investigated the ability of BPD and LED to cause inhibition of cell growth in canine glioma and human glioma cell lines, in vitro. The biodistribution of BPD labeled with 111In-BPD in mice with subcutaneous and intracerebral gliomas and canines with brain tumors was studied. RESULTS: The in vivo canine study resulted in a maximal tolerated dose of 0.75 mg/kg of BPD and 100 J/cm(2) of LED light for normal brain tissue. The in vitro study demonstrated 50% growth inhibition for canine and human glioma cell lines of 10 and 4 ng/ml, respectively. The mucine study using 111In-BPD showed a tumor to normal tissue ratio of 12:1 for intracerebral tumors and 3.3:1 for subcutaneous tumors. Nuclear scans of canines with brain tumors showed uptake into tumors to be maximal from 3 to 5 h. CONCLUSION: Our study supports that BPD and LED light sources when used at appropriate drug and light doses limit normal brain tissue toxicity at doses that can cause significant glioma cell toxicity in vitro. In addition, there is higher BPD uptake in brain tumors as compared to normal brain in a mouse glioma model. These findings make BPD a potential new-generation photosensitizer for the treatment of childhood posterior fossa tumors as well as other malignant cerebral pathology.

Intramyocardial arterial cushions of coronary vessels in animals and humans: morphology, occurrence and relation to heart disease.

The existence of coronary endoarterial cushions (CEC) in the human heart as nonpathological, functional entities has been debated, and CEC have been sparsely reported in animals. Arterial cushions are localized thickenings that protrude into the lumen of specific arteries. We have identified CEC in the rhesus monkey, dog, sheep, goat, pig, rabbit and rat, and in the human heart. Two distinct types are described: the ovoid CEC arranged singly, in pairs, or in groups of three to four, and the less common polypoid CEC seen primarily in humans. The highest incidence of CEC in rabbits and humans was in the left ventricle in arteries 150-488 microns in diameter. Light and electron microscopy demonstrated intimal location with smooth muscle cells surrounded by ground substance, collagen and elastin fibers in a highly organized pattern. Nerve fibers identified by their immunoreactivity with antiserum to the vasodilatory calcitonin-gene-related peptide contacted the CEC along the tunica media and were occasionally seen within CEC. Arrangement and histological composition of CEC suggest a role in the regulation of local blood flow and myocardial perfusion. In human hearts, the CEC density index correlated highly with the degree of heart disease. In subjects with high heart disease rating, increased connective tissue, lipid-like infiltration and calcification was seen within CEC, and foam cells were present in CEC of obese rabbits. This suggests that CEC in coronary arteries could be predisposed sites of atherosclerosis, and that injured CEC can cause coronary artery spasm and ischemia. We conclude that CEC occur in animals and humans as innervated intimal smooth muscle cushions that might have a role in myocardial perfusion and heart disease.

Efficacy of ivermectin against benzimidazole-resistant Nematodirus spathiger in sheep.

Eighteen helminth-free lambs were randomly allocated to six groups of three. Each lamb was dosed with 3300 infective larvae pooled from two isolates of Nematodirus spathiger known to be benzimidazole resistant. One lamb from each group was treated with oral ivermectin, one with oral oxfendazole and one left untreated 21 days after infection. All lambs were humanely killed 14 days later and small intestine worm counts performed. No Nematodirus were found in the ivermectin-treated lambs. Nematodirus numbers were reduced by 13% in oxfendazole-treated lambs relative to the control lambs.

Evaluation of the efficacy of doramectin against an artificial infection of Dictyocaulus viviparus in calves.

Three groups of eight Friesian calves, reared parasite-free, were experimentally infected with 1000 infective larvae of Dictyocaulus viviparus. Two groups were injected subcutaneously with 1% doramectin at 0.2 mg/kg body weight, one group 5 days after infection and the other 25 days after infection. A third group served as untreated controls. Faecal samples were examined for lungworm larvae on days 28, 32, 33, 34 and 35 after infection; the calves were killed and necropsied 39 or 40 days after infection and any lungworms present recovered and counted. Doramectin proved 100% effective against both 5-day-old and mature D. viviparus infections.

Multiple resistance in goat-derived Ostertagia and the efficacy of moxidectin and combinations of other anthelmintics.

Faecal egg count reduction tests were used to identify a strain of Ostertagia circumcincta/trifurcata complex in goats which was resistant to: ivermectin (at 0.2 mg/kg and 0.4 mg/kg orally), oxfendazole (at 5 mg/kg orally), levamisole (at 12 mg/kg orally) and fenbendazole (at 5 mg/kg orally) combined with levamisole (at 9.4 mg/kg orally). The percentage reductions achieved in these faecal egg count reduction tests were respectively 27%, 83%, 82%, 79% and 82%. Moxidectin (at 0.2 mg/kg by subcutaneous injection), fenbendazole (at 10 mg/kg orally) combined with levamisole (at 18.8 mg/kg orally), ivermectin (at 0.4 mg/kg orally) combined with oxfendazole (at 10 mg/kg orally) and ivermectin (at 0.4 mg/kg orally) combined with levamisole (at 12 mg/kg orally) were effective in removing these nematodes in goats as determined by faecal egg count reduction tests. These drenches achieved reductions of 100%, 100%, 98% and 100% respectively.