A diabetic foot ulcer treated with hydrogel and hyperbaric oxygen therapy: a case study.

This study reports on the case of an elderly patient, with diabetes, and a bullous wound on the left big toe that led to an amputation of the first and second left toes. The amputation was because of deep injury as it was not able to heal with a conventional treatment. After completing the normal treatment and the removal of a bacterial infection in the lesion, the patient underwent a treatment that was based on a hydrogel gel (0.9% saline solution) and hyperbaric oxygen therapy (HBOT). After 60 sessions of the therapy, almost complete closure of the wound was observed. There were no reports of discomfort or infection during the treatment. After seven months of treatment almost complete healing was observed with no infection. This treatment appears to be effective and should be recommended for the treatment of DFUs.

Spinal blockage of P/Q- or N-type voltage-gated calcium channels modulates functional and symptomatic changes related to haemorrhagic cystitis in mice.

BACKGROUND AND PURPOSE: Spinal voltage-gated calcium channels (VGCCs) are pivotal regulators of painful and inflammatory alterations, representing attractive therapeutic targets. We examined the effects of epidural administration of the P/Q- and N-type VGCC blockers Tx3-3 and Phα1ß, respectively, isolated from the spider Phoneutria nigriventer, on symptomatic, inflammatory and functional changes allied to mouse cyclophosphamide (CPA)-induced haemorrhagic cystitis (HC). The effects of P. nigriventer-derived toxins were compared with those displayed by MVIIC and MVIIA, extracted from the cone snail Conus magus. EXPERIMENTAL APPROACH: HC was induced by a single i.p. injection of CPA (300 mg·kg(-1) ). Dose- and time-related effects of spinally administered P/Q and N-type VGCC blockers were assessed on nociceptive behaviour and macroscopic inflammation elicited by CPA. The effects of toxins were also evaluated on cell migration, cytokine production, oxidative stress, functional cystometry alterations and TRPV1, TRPA1 and NK1 receptor mRNA expression. KEY RESULTS: The spinal blockage of P/Q-type VGCC by Tx3-3 and MVIIC or N-type VGCC by Phα1ß attenuated nociceptive and inflammatory events associated with HC, including bladder oxidative stress and cytokine production. CPA produced a slight increase in bladder TRPV1 and TRPA1 mRNA expression, which was reversed by all the toxins tested. Noteworthy, Phα1ß strongly prevented bladder neutrophil migration, besides HC-related functional alterations, and its effects were potentiated by co-injecting the selective NK1 receptor antagonist CP-96345. CONCLUSIONS AND IMPLICATIONS: Our results shed new light on the role of spinal P/Q and N-type VGCC in bladder dysfunctions, pointing out Phα1ß as a promising alternative for treating complications associated with CPA-induced HC.

Antiallodynic effect and side effects of Phα1ß, a neurotoxin from the spider Phoneutria nigriventer: comparison with ω-conotoxin MVIIA and morphine.

Phα1ß is a potent toxin obtained from the spider Phoneutria nigriventer that blocks neuronal voltage-sensitive Ca(2+) channels. This study compared the antiallodynic effects of Phα1ß, ω-conotoxin MVIIA and morphine in mice and their side effects in rats. Mechanical allodynia was measured in mice receiving single intrathecal administration of Phα1ß, ω-conotoxin MVIIA or morphine before or after the incisional plantar procedure. The effect of the treatments on cardiovascular profile and global neurological were evaluated in rats. The expression of pro or anti-inflammatory cytokines of human polymorph mononuclear cells was also evaluated. Preemptive use of ω-conotoxin MVIIA (1.0 or 10 pmol/site) or morphine (1000 pmol/site) induced shorter antiallodynic effect than Phα1ß (100 pmol/site) in mice. Post-incision administration of Phα1ß (200 pmol/site) induced longer mechanical antiallodynic effect than ω-conotoxin MVIIA (1.0 or 10 pmol/site) or morphine (1000 pmol/site). Intrathecal injection of Phα1ß (200 pmol/site) and morphine (433 pmol/site) did not change while ω-conotoxin MVIIA (100 pmol/site) increased the heart rate in rats 3 h after its administration. Phα1ß (200 pmol/site), ω-conotoxin MVIIA (100 pmol/site) and morphine (433 pmol/site) did not change mean arterial pressure 0.5 and 3 h after their administration. The treatments did not alter neurological performance assessed by global neurological evaluation and open-field test. The tested drugs did not induced expression of pro or anti-inflammatory cytokines in CD4 monocytes. In conclusion, preemptive administration Phα1ß in mice induced longer antiallodynic effect than ω-conotoxin MVIIA and morphine. Phα1ß also induced a longer mechanical antiallodynic effect than ω-conotoxin MVIIA and morphine when used after the surgical incision. The present results suggest that Phα1ß has a potential application in the management of postoperative pain with low side effects.

A pyrazolyl-thiazole derivative causes antinociception in mice.

The present study investigates the antinociceptive effect of the pyrazolyl-thiazole derivative 2-(5-trichloromethyl-5-hydroxy-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)-4-(4-bromophenyl)-5-methylthiazole (B50) in mice. Male albino Swiss mice (30-40 g) were used in the acetic acid-induced abdominal writhes and tail-immersion tests. B50 caused dose-dependent antinociception (8, 23 and 80 micromol/kg, s.c.) in the acetic acid writhing assay (number of writhes: vehicle: 27.69 +/- 6.15; B50 (8 micromol/kg): 16.92 +/- 3.84; B50 (23 micromol/kg): 13.85 +/- 3.84; B50 (80 micromol/kg): 9.54 +/- 3.08; data are reported as means +/- SEM for 9 animals per group). On the other hand, B50 did not cause antinociception in the tail immersion assay. Naloxone (2.75 micromol/kg, s.c.) prevented B50-induced antinociception (number of writhes: vehicle-saline: 31.11 +/- 3.15; vehicle-naloxone: 27.41 +/- 3.70; B50 (80 micromol/kg)-saline: 8.70 +/- 3.33; B50 (80 micromol/kg)-naloxone: 31.84 +/- 4.26; morphine-saline: 2.04 +/- 3.52; morphine-naloxone: 21.11 +/- 4.26; 8-9 animals per group). The removal of the methyl group of the thiazole ring of B50 or substitution of the bromo substituent with the methyl at position 4 of the phenyl group, which is attached to the thiazole ring of B50, resulted in loss of activity, suggesting that these substituents are important for antinociceptive activity. B50 had no effect on spontaneous locomotion or rotarod performance, indicating that the antinociceptive effect of B50 is not related to nonspecific motor effects. The antinociceptive profile of B50 seems to be closer to nonsteroidal anti-inflammatory drugs than to classic opioid agents, since it had no analgesic effect in a thermally motivated test.