Huse Kamencic

Quercetin Promotes Functional Recovery Following Acute Spinal Cord Injury

We tested the hypothesis that quercetin, a potent Fe(2+)-chelating flavonoid, would decrease secondary damage following spinal cord trauma. MRI studies using the relaxation of the T1 proton signal caused by Fe(2+) ions and the dose-dependent reversal of this effect by addition of quercetin in aqueous solution were used to guide us to the dosage of quercetin to be used in animal experimentations. Forty-four male Wistar rats were used in two experimental series to test the hypothesis that administration of quercetin improves recovery of motor function after acute traumatic spinal cord injury. Animals were subjected to laminectomy and subjected to an extradural 40-g force clip compression for 5 sec at T7. Quercetin or saline was administered intraperitoneally 1 h after injury and then every 12 hr thereafter. Recovery of motor function was assessed using BBB scores at weekly intervals for 4 weeks. A dose of 2.5 micromoles quercetin/kg body weight did not result in significantly better functional outcome, whereas doses ranging from 5 to 100 micromoles quercetin/kg body weight resulted in a significantly better functional outcome with half or more of the animals walking, although with deficit; in contrast, no animals walked in the group of saline-treated animals. No significant differences in behavioral outcome were seen amongst the doses ranging from 5 to 100 micromol/kg, nor was there a difference if animals were treated for 4 or 10 days. Therapeutic outcome was coincident with more efficient iron clearance, suggesting that one possible mechanism whereby quercetin decreases secondary damage is through iron chelation.

Pentoxifylline After Conservative Surgery for Endometriosis: A Randomized, Controlled Trial

STUDY OBJECTIVE To compare outcomes after conservative surgery for endometriosis with and without pentoxifylline and to assess the efficacy of pentoxifylline in preventing recurrence of endometriosis after conservative surgery. DESIGN Parallel-group, randomized, controlled trial (Canadian Task Force classification I). SETTING Tertiary care hospital. PATIENTS Women undergoing conservative surgery for endometriosis. INTERVENTIONS Laparoscopic conservative surgery for endometriosis was completed by a single surgeon (J.A.T.), and all suspected endometriotic lesions were widely excised using monopolar coagulation and scissors. All specimens were submitted to pathology for confirmation of the diagnosis. Randomization to the treatment or control groups was completed preoperatively in the outpatient surgery unit by drawing colored marbles. A preoperative visual analog pain scale (VAS) was completed. After surgery, patients were discharged home with prescriptions for naproxen, hydromorphone, and pentoxifylline. MEASUREMENTS AND MAIN RESULTS Visual analog scale scoring was completed monthly by each patient, and each patient was seen monthly for review and pelvic examination. Analgesic use was recorded daily using an individual medication log. Ongoing treatment choice after completion of the 3-month follow-up was recorded. The relationship between the group receiving pentoxifylline and the control group as well as analysis of the VAS scores at time of surgery and 1, 2, and 3 months postoperatively was determined using a covariate mixed-model ANOVA. Forty-nine patients were enrolled in the trial. One patient became pregnant before surgery, and 1 patients chart was not available for analysis. Of the 47 who underwent conservative surgery for endometriosis, 9 (19%) had no endometriosis noted in the pathology specimens submitted. Two patients withdrew from the trial after surgery, and 2 patients were lost to follow-up after relocating to a different city. Nineteen women completed the 3-month follow-up in the control group, 15 in the group receiving pentoxifylline. The mean age, gravidity, parity, body mass index, previous surgery for endometriosis, menstrual cycle, and preoperative analgesic use did not differ significantly between the control and treatment groups. The time to complete the conservative surgery did not vary between the 2 groups. There were no intraoperative complications: two patients were admitted postoperatively, one for nausea and vomiting, one for pain that resolved 24 hours after admission. The VAS scores did not differ at the time of surgery; and in both the control and the pentoxifylline groups, there was significant improvement at each monthly interval (p <.05). The patients receiving pentoxifylline had significantly better VAS scores at 2 and 3 months after surgery (p <.03). CONCLUSIONS The use of pentoxifylline after conservative surgery for endometriosis resulted in improved VAS scores at 2 and 3 months after the procedure when compared with patients having conservative surgery only. The longer-term use of pentoxifylline after conservative surgery may improve long-term outcomes after surgical treatment for endometriosis.

Tumour necrosis factor-α (TNF-α) transgene-expressing dendritic cells (DCs) undergo augmented cellular maturation and induce more robust T-cell activation and anti-tumour immunity than DCs generated in recombinant TNF-α

Tumour antigen presentation by dendritic cells (DCs) to T cells in lymphoid organs is crucial for induction of anti‐tumour immune responses. It has been previously reported that tumour necrosis factor‐α (TNF‐α) is required for DC activation and subsequent induction of optimal immune responses, and thus DCs for anti‐tumour vaccination are often generated by culture in exogenous TNF‐α. In the present study, we investigated the effect on anti‐tumour immunity of vaccination with Mut1 tumour peptide‐pulsed DCs engineered to express a TNF‐α transgene. Our data shows that transfection of DCs with recombinant adenovirus AdV‐TNF‐α resulted in greater maturation of the DCs than occurred with control DCs cultured in exogenous TNF‐α, as determined by up‐regulated expression of pro‐inflammatory cytokines (e.g. interleukins 1β and 18), chemokines [e.g. interferon‐γ‐inducible protein‐10 and macrophage inflammatory protein‐1β (MIP‐1β)], the CC chemokine receptor CCR7, and immunologically important cell surface molecules (CD40, CD86 and intercellular adhesion molecule‐1). These transgenic DCs stimulated stronger allogeneic T‐cell responses in vitro and T‐cell activation in vivo; displayed 2·4‐fold enhanced chemotactic responses to the MIP‐3βin vitro (P<0·05); and, perhaps most importantly, trafficked into the draining lymph nodes dramatically (seven‐fold, P<0·01) more efficiently than the control DCs. Our data also demonstrate that vaccination of mice with Mut1 peptide‐pulsed, AdV‐TNF‐α‐transfected DCs stimulated more efficient in vitro Mut1‐specific CD8+ cytotoxic T‐cell responses and solid tumour immunity in vivo, when compared to the in vitro TNF‐α‐cultivated DCs. Thus, DCs engineered to secrete TNF‐α may offer a new strategy in DC cancer vaccines.

Assessment of Costs Associated With OutpatientTotal Laparoscopic Hysterectomy

OBJECTIVE To assess the costs associated with the performance of outpatient total laparoscopic hysterectomy. METHODS This was a retrospective cohort study involving 224 consecutive patients undergoing total laparoscopic hysterectomy (TLH) by a single surgeon in the Regina General Hospital. Outcomes included costs associated with the initial procedure as well as those associated with any intraoperative or postoperative complications. RESULTS The mean age of the patients was 42.7 years. The mean uterine weight was 205 grams (range 69-1163 g), the mean operating time was 79 minutes, and the mean blood loss was 89 cc. The mean postoperative stay in the day surgery unit (DSU) was 354 minutes. Ten patients required admission from the DSU, and nine patients were admitted more than 24 hours after surgery. The total number of admission days was 24, which cost 21,900 US dollars. The total cost of all disposables was 127,373 US dollars and the cost associated with the stays in day surgery was 89,600 US dollars. The total cost for the 224 TLH procedures was 238,573 US dollars, and the average cost per TLH was 1065 US dollars. CONCLUSION Outpatient TLH can be completed safely and with costs that are lower than those incurred by patients having short-stay vaginal hysterectomy in our institution. Outpatient TLH offers the opportunity to save health care costs and a procedure with excellent results.

Sulfur amino acid deficiency depresses brain glutathione concentration.

Dietary sulfur amino acid content is a major determinant of glutathione concentration in some tissues. We examined whether brain glutathione (GSH), a key component of antioxidant defense important for minimizing ischemic injury, was also responsive to short-term sulfur amino acid deficiency. Female Long-Evans adult rats were fed a sulfur-deficient L-amino acid defined diet for five days; the control diet was supplemented with L-cystine and L-methionine (n=6). Sulfur amino acid deficiency was confirmed by a reduction in liver cysteine and GSH concentrations, marked decreases in food intake, and weight loss. GSH concentration analyzed by reverse-phase high performance liquid chromatography was significantly depressed in the neocortex and thalamus of deficient rats. Brain cysteine was not decreased in a parallel manner. Classical glutathione peroxidase activity was increased in the liver and brain of sulfur amino acid deficient rats. This suggests an upregulation of antioxidant defense but these findings may be complicated by alterations in tissue composition. The depletion of brain GSH by a reduced supply of dietary precursors may be important during brain ischemia when the rate of GSH utilization and the need for synthesis are increased.

Expect the Unexpected: A Case of Pelvic Splenosis

The patient gave consent for total laparoscopic hysterectomy with removal of the mass. At laparoscopy several soft tissue masses were seen throughout the abdomen and pelvis (Figure). One was excised (white arrow) and sent for frozen section, which indicated benign tissue. Hysterectomy was completed and the remaining splenules were left intact (black arrows). Formal histologic assessment confirmed splenosis.

S'attendre à l'inattendu : Cas de splénose pelvienne

U femme de 35 ans, gravida 3 para 3, presentait une menometrorragie. L’echographie pelvienne revelait la presence d’une masse extra-ovarienne de 4 cm sur 3 cm. Un tomodensitogramme subsequent a egalement revele la presence de multiples nodules de tissu mou partout dans le bassin. Nous avons alors estime que ces nodules cadraient bien avec la presence d’une splenose, puisque la patiente avait connu une rupture splenique traumatique (s’etant suivie d’une splenectomie) 25 ans auparavant.