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Biomedical subjects

Battista Borghi

Publications and source records attributed to Battista Borghi.

13 recordsLinked to original sources

Alpha-tocopheryl succinate induces DR4 and DR5 expression by a p53-dependent route: implication for sensitisation of resistant cancer cells to TRAIL apoptosis.

We evaluated the ability of alpha-tocopheryl succinate (alpha-TOS) to sensitise TRAIL-resistant malignant mesothelioma (MM) cells to TRAIL-induced apoptosis. We show that alpha-TOS activates expression of DR4/DR5 in a p53-dependent manner and re-establishes sensitivity of resistant MM cells to TRAIL-mediated apoptosis, as documented in p53wt MM cells but not in their p53null counterparts. MM cells selected for TRAIL resistance expressed low cell surface levels of DR4 and DR5. Treatment with sub-lethal doses of alpha-TOS restored expression of DR4 and DR5. The ability of alpha-TOS to modulate expression of pro-apoptotic genes may play a role in sensitisation of tumour cells to immunological stimuli.

Apoptosis↗

Alpha-tocopheryl succinate alters cell cycle distribution sensitising human osteosarcoma cells to methotrexate-induced apoptosis.

alpha-Tocopheryl succinate (alpha-TOS) exerts pleiotrophic responses in malignant cells leading to cell cycle arrest, differentiation and apoptosis. We tested the ability of alpha-TOS to induce apoptosis or cell cycle perturbation in three human osteosarcoma (OS) cell lines which differ in their pRB and p53 status. We found high levels of apoptosis in OS cells carrying wild-type p53 gene when exposed to alpha-TOS, while the mutant p53 cells were resistant. A S/G2 transition arrest was observed in two OS cell lines exposed to alpha-TOS, which sensitised them to methotrexate, an agent whose activity is cell cycle-dependent. We propose that alpha-TOS may be used as a drug or an adjuvant for treatment of osteosarcomas.

Apoptosis↗

alpha-Lipoic acid supplementation inhibits oxidative damage, accelerating chronic wound healing in patients undergoing hyperbaric oxygen therapy.

Hyperbaric oxygen (HBO) therapy is successfully used for the treatment of a variety of conditions. However, prolonged exposure to high concentrations of oxygen induces production of reactive oxygen species, causing damage to the cells. Thus, antioxidant supplementation has been proposed as an adjuvant to attenuate such deleterious secondary effects. We evaluated the effects of alpha-lipoic acid (LA) in patients affected by chronic wounds undergoing HBO treatment. LA supplementation efficiently reduces both the lipid and DNA oxidation induced by oxygen exposure. LA exerted its antioxidant activity by directly interacting with free radicals or by recycling vitamin E. An inhibitory effect of LA on the pro-inflammatory cytokine interleukin-6 was observed. Taken together, we demonstrated an adjuvant effect of LA in HBO therapy used for impaired wound healing treatment. We propose that LA may be used to further promote the beneficial effects of HBO therapy.

Administration, Oral↗

Alpha-tocopheryl succinate induces cytostasis and apoptosis in osteosarcoma cells: the role of E2F1.

Alpha-tocopheryl succinate (alpha-TOS), a redox-inactive analog of vitamin E, induces cell cycle arrest, differentiation, and triggers apoptosis. We examined the ability of alpha-TOS to induce cytostasis and/or apoptosis in two human osteosarcoma cell lines, which carry wild-type pRb but differ in the p53 status. In the wt-p53 cells, alpha-TOS induced apoptosis, which was associated with p53 activation and enhanced E2F1 expression. Mutant p53 cells failed to undergo apoptosis when challenged with alpha-TOS. The cell growth arrest after alpha-TOS treatment was associated with a reduced expression of E2F1. Knocking down E2F1 rendered the alpha-TOS-sensitive cells rather resistant to the apoptotic stimulus inducing a marked and prolonged cell growth arrest. We conclude that alpha-TOS induces cell growth arrest or apoptosis involving E2F1.

Apoptosis↗

Effect of different anesthesia techniques on red blood cell endogenous recovery in hip arthroplasty.

STUDY OBJECTIVE: To compare the magnitude of postoperative red blood cell (RBC) recovery with 3 different anesthetic techniques, general anesthesia (GA), epidural anesthesia (EA) alone, and the combination of these 2 techniques (CA), in patients undergoing total hip arthroplasty. DESIGN: Randomized, controlled study. SETTING: Seven university or hospital departments of anesthesia. PATIENTS: Two hundred ten patients with American Society of Anesthesiologists physical status I to III were randomly selected to receive EA, GA, or CA. INTERVENTION: Patients undergoing total hip replacement were randomly assigned to 3 statistically comparable groups based on the type of anesthesia received: GA, EA, and CA groups. MEASUREMENTS AND MAIN RESULTS: Intra- and postoperative blood loss was evaluated as either compensated or noncompensated blood loss by using Nadler's formula. The intra- and postoperative bleeding, referred to as compensated blood loss, was similar among groups. The circulating RBC mass, noncompensated blood loss, dropped on the first postoperative day to a similar extent among the groups. The endogenous recovery of the RBC is carried out on the fifth day after surgery in patients who underwent EA, whereas no RBC recovery was observed in those who had received GA alone or GA combined with EA. CONCLUSIONS: Patients who had received EA had a faster recovery of the circulating erythrocyte mass than those who had had GA or CA. The presence of nitrous oxide in the anesthetic gas mixture might inhibit erythropoiesis by altering vitamin B(12) functions.

Adult↗

A prospective, randomized evaluation of the effects of epidural needle rotation on the distribution of epidural block.

UNLABELLED: We evaluated the effects of turning the tip of the Tuohy needle 45 degrees toward the operative side before threading the epidural catheter (45 degrees -rotation group, n = 24) as compared to a conventional insertion technique with the tip of the Tuohy needle oriented at 90 degrees cephalad (control group, n = 24) on the distribution of 10 mL of 0.75% ropivacaine with 10 microg sufentanil in 48 patients undergoing total hip replacement. The catheter was introduced 3 to 4 cm beyond the tip of the Tuohy needle. A blinded observer recorded sensory and motor blocks on both sides, quality of analgesia, and volumes of local anesthetic used during the first 48 h of patient-controlled epidural analgesia. Readiness to surgery required 21 +/- 6 min in the control group and 17 +/- 7 min in the 45 degree-rotation group (P > 0.50). The maximum sensory level reached on the operative side was T10 (T10-7) in the control group and T9 (T10-6) in the 45 degree-rotation group (P > 0.50); whereas the maximum sensory level reached on the nonoperative side was T10 (T12-9) in the control group and L3 (L5-T12) in the 45 degree-rotation group (P = 0.0005). Complete motor blockade of the operative limb was achieved earlier in the 45 degree-rotation than in the control group, and motor block of the nonoperative side was more intense in patients in the control group. Two-segment regression of sensory level on the surgical side was similar in the two groups, but occurred earlier on the nonoperative side in the 45 degree-rotation group (94 +/- 70 min) than in the control group (178 +/- 40 min) (P = 0.0005). Postoperative analgesia was similar in the 2 groups, but the 45 degree-rotation group consumed less local anesthetic (242 +/- 35 mL) than the control group (297 +/- 60 mL) (P = 0.0005). We conclude that the rotation of the Tuohy introducer needle 45 degrees toward the operative side before threading the epidural catheter provides a preferential distribution of sensory and motor block toward the operative side, reducing the volume of local anesthetic solution required to maintain postoperative analgesia. IMPLICATIONS: Turning the Tuohy introducer needle 45 degrees toward the operative side before threading the epidural catheter is a simple maneuver that produces a preferential distribution of epidural anesthesia and analgesia toward the operative side, minimizing the volume of local anesthetic required to provide adequate pain relief after total hip arthroplasty.

Aged↗

Unilateral spinal block for outpatient knee arthroscopy: a dose-finding study.

STUDY OBJECTIVE: To evaluate the onset time, success rate, and recovery profile of unilateral spinal anesthesia produced with 4 mg, 6 mg, and 8 mg of 0.5% hyperbaric bupivacaine. DESIGN: Prospective, randomized, blinded study. SETTING: Outpatient anesthesia unit at a University Hospital. PATIENTS: 90 ASA physical status I and II outpatients, who were scheduled for elective knee arthroscopy. INTERVENTIONS: After standard intravenous midazolam premedication (0.05 mg/kg) and crystalloid infusion (7 mL/kg) were given, patients were placed in the lateral decubitus position on the operative side, and randomly allocated to receive spinal block with either 4 mg (Group 4, n = 30), 6 mg (Group 6, n = 30), or 8 mg (Group 8, n = 30) of 0.5% hyperbaric bupivacaine injected slowly (3 mL/min) with the needle orifice directed toward the dependent side using a 25-gauge Whitacre needle. The lateral decubitus position was maintained for 15 minutes. MEASUREMENTS AND MAIN RESULTS: The onset time of surgical block was 13 +/- 5 minutes in Group 4 and 10 +/- 4 minutes in Group 6 (p = 0.006), and 9 +/- 4 minutes in Group 8 (p = 0.002). The maximum level of sensory block on the operative and nonoperative sides was, respectively, T(10) (T(12)-T(6)) and / (/-L(2)) in Group 4 (p = 0.0005), T(8) (T(12)-T(6)) and / (/-L(5)) in Group 6 (p = 0.0005), and T(7) (T(12)-T(5)) and / (/-T(10)) in Group 8 (p = 0.0005). A strictly unilateral sensory block was observed in 27 Group 4 patients (90%), 28 Group 6 patients (93%) and 23 Group 8 patients (77%) (p = 0.28). Complete unilateral motor block was observed in 29 Group 4 patients (97%), 28 Group 6 patients (93%), and 28 Group 8 patients (93%) (p = 0.80). No failed blocks were reported. Complete regression of spinal anesthesia required 71 +/- 20 minutes in Group 4 (range: 40 to 110 min), 82 +/- 25 minutes in Group 6 (range: 30 to 160 min), and 97 +/- 37 minutes in Group 8 (range: 50 to 120 min) (p = 0.003). CONCLUSIONS: Hyperbaric bupivacaine 4 mg injected slowly through pencil-point directional needles in patients who are maintained in the lateral decubitus position for 15 minutes provided a surgical block that was mostly restricted to the operative side and adequate to perform knee arthroscopy, with a faster recovery profile than when a 6 mg or 8 mg dose was used.

Adult↗

Lymphocyte DNA damage precedes DNA repair or cell death after orthopaedic surgery under general anaesthesia.

Anaesthetics have gained a lot of attention for their potential mutagenic/carcinogenic effects. In the present study we have investigated the genotoxicity of the inhalation anaesthetic sevoflurane on DNA of lymphocytes isolated from 20 patients undergoing orthopaedic surgery. The genotoxicity of the anaesthetic was studied by assaying DNA damage, apoptosis, DNA repair enzyme activity and GSH content in peripheral lymphocytes before, 15 min after anaesthesia and 24 h after surgery. Lymphocytes isolated 15 min after anaesthesia showed an increase in oxidized purine and pyrimidine bases without DNA strand break formation. DNA strand breaks occurred on the first post-operative day, associated with an enhancement of DNA repair activity and a decrease in GSH. Formation of strand breaks could be the consequence of DNA repair activity. In fact, at 24 h after surgery most of the oxidized DNA bases were repaired. When DNA damage was not repaired, activation of the cell cycle checkpoint protein p53 could lead to apoptosis. An altered redox status may contribute to lymphocytopenia due to an apoptotic event as a consequence of surgical trauma. The presence of apoptotic cells at 1 day after surgery could support the hypothesis that highly damaged peripheral lymphocytes are committed to undergo programmed cell death if the damage is not repaired. In conclusion, the actual risk from anaesthesia is presumably extremely small. However, these findings contribute to our understanding of the regulation of DNA damage/repair and cell death.

Adult↗

Interscalene brachial plexus anesthesia and analgesia for open shoulder surgery: a randomized, double-blinded comparison between levobupivacaine and ropivacaine.

UNLABELLED: We compared the onset time and quality of interscalene brachial plexus block produced with levobupivacaine and ropivacaine in 50 patients undergoing open shoulder surgery randomly allocated to receive 30 mL of 0.5% levobupivacaine (n = 25) or 0.5% ropivacaine (n = 25) injected through a 20-gauge catheter placed into the interscalene sheath using a 18-gauge insulated and stimulating Tuohy introducer. The block was also prolonged after surgery using a patient-controlled interscalene analgesia with 0.125% levobupivacaine or 0.2% ropivacaine, respectively (basal infusion rate, 6 mL/h; bolus, 2 mL; lockout period, 15 min; maximum boluses per hour, three). Three patients (two with levobupivacaine [8%] and one with ropivacaine [4%]) failed to achieve surgical block within 45 min after the injection and were excluded. The onset time of surgical block was 20 min (10-40 min) with levobupivacaine and 20 min (5-45 min) with ropivacaine (P = 0.53). Rescue intraoperative analgesia (0.1 mg of fentanyl IV) was required in eight patients in each group (34%) (P = 0.99). Forty-two patients completed the 24-h postoperative infusion (22 with levobupivacaine and 20 with ropivacaine). Postoperative analgesia was similarly effective in both groups. Total consumption of local anesthetic infused during the first 24 h was 147 mL (144-196 mL) with levobupivacaine and 162 mL (144-248 mL) with ropivacaine (P = 0.019), with a ratio between boluses received and requested of 0.8 (0.4-1.0) and 0.7 (0.4-1.0), respectively (P = 0.004). The degree of motor block of the operated limb was deeper with levobupivacaine than ropivacaine when starting postoperative analgesia; however, no further differences in degree of motor function were observed between the two groups. We conclude that 30 mL of levobupivacaine 0.5% induces an interscalene brachial plexus anesthesia of similar onset and intensity as the one produced by the same volume and concentration of ropivacaine. Postoperative interscalene analgesia with 0.125% levobupivacaine results in similar pain relief and recovery of motor function with less volume of local anesthetic than with 0.2% ropivacaine. IMPLICATIONS: This prospective, randomized, double-blinded study demonstrates that 30 mL of 0.5% levobupivacaine produces an interscalene brachial plexus block of similar onset and quality as the one produced by the same volume of 0.5% ropivacaine. When prolonging the block after surgery, 0.125% levobupivacaine provides adequate pain relief and recovery of motor function after open shoulder surgery, with less volume infused during the first 24 h after surgery than 0.2% ropivacaine.

Adolescent↗

Frequency of hypotension and bradycardia during general anesthesia, epidural anesthesia, or integrated epidural-general anesthesia for total hip replacement.

STUDY OBJECTIVE: To evaluate the frequency of hypotension and bradycardia during integrated epidural-general anesthesia as compared with general anesthesia or epidural anesthesia alone. DESIGN: Prospective, randomized, open, multicenter study. SETTING: Inpatient anesthesia at 7 University or Hospital Departments of anesthesia. PATIENTS: 210 ASA physical status I, II, and III patients undergoing elective total hip replacement. INTERVENTIONS: Using a balanced randomization method, each hospital enrolled 30 consecutive patients who received integrated epidural-general anesthesia, epidural anesthesia, or general anesthesia. MEASUREMENTS AND MAIN RESULTS: Occurrence of clinically relevant hypotension (systolic arterial blood pressure (BP) decrease >30% from baseline), or bradycardia (heart rate (HR) <45 bpm) requiring pharmacologic treatment were recorded, as well as routine cardiovascular parameters. Clinically relevant hypotension during induction of nerve block was reported in 13 patients receiving epidural block (18%) and 16 patients receiving epidural-general anesthesia (22%) (p = 0.67). Subsequently, 22 of the remaining 54 patients in the epidural-general anesthesia group (41%) developed hypotension after the induction of general anesthesia, as compared with 16 patients of the general anesthesia group (23%) (p = 0.049). No differences in HR or in frequency of bradycardia were observed in the three groups. CONCLUSIONS: The induction of general anesthesia in patients with an epidural block up to T10 increased the odds of developing clinically relevant hypotension as compared with those patients who received no epidural block, and was associated with a twofold increase of the odds of hypotension as compared with the use of epidural anesthesia alone.

Aged↗

Outpatient lower extremity infusions.

The considerable development of ambulatory surgery has led to an increase in the number of lower extremity procedures performed in an outpatient setting. More recently, the availability of disposable pumps has allowed us to extend the indications of continuous nerve blocks for ambulatory post-operative pain management. Indications for lumbar plexus continuous blocks include anterior cruciate ligament (ACL) reconstruction and patella repairs as well as frozen knee, whereas continuous sciatic blocks are indicated for major foot and ankle surgery. Different modes of local anaesthetic administration have been applied, including the use of repeated bolus, continuous administration and, more recently, patient-controlled perineural infusions. This latter technique seems to be the preferred mode because it offers the advantage of tailoring the amount of local anaesthetics, mostly 0.2% ropivacaine, to the individual need and also maximizes the duration of infusion for a given volume of local anaesthetic. Although the preliminary reports indicate that lower extremity continuous blocks provide effective post-operative ambulatory analgesia and are safe, especially as a part of a multimodal approach, appropriate training in these techniques represents one of the most important limiting factors of the placement of perineural catheters. Additional research is required to determine the optimal conditions in which these techniques are indicated.

Ambulatory Surgical Procedures↗

A double-blinded, randomized comparison of either 0.5% levobupivacaine or 0.5% ropivacaine for sciatic nerve block.

UNLABELLED: To compare intraoperative and postoperative clinical properties of levobupivacaine and ropivacaine for sciatic nerve block, 50 ASA physical status I and II patients undergoing hallux valgus repair received a femoral nerve block with 15 mL of 2% mepivacaine. They were then randomly allocated in a double-blinded fashion to receive a sciatic nerve block with either 0.5% levobupivacaine (n = 25) or 0.5% ropivacaine (n = 25). An independent blinded observer evaluated the onset time of surgical anesthesia as well as the quality of the surgical block and postoperative analgesia. The median (range) onset time of surgical block at the sciatic nerve distribution was 30 min (5-60 min) with levobupivacaine and 15 min (5-60 min) with ropivacaine (P = 0.63). Four patients (two patients in each group) received a supplementary ankle block by the surgeon just before the beginning of surgery. All four patients also received IV fentanyl supplementation, but in three of them, propofol infusion was required to complete surgery (two in the Levobupivacaine group [8%] and one in the Ropivacaine group [4%]; P = 0.99). In six patients of the Levobupivacaine group (24%) and five patients of the Ropivacaine group (20%), IV fentanyl supplementation was required to complete surgery (P = 0.99). No differences in the time to recovery of sensory and motor function were observed between the two groups, whereas median (range) duration of postoperative analgesia was 16 h (8-24 h) with levobupivacaine and 16 h (8-24 h) with ropivacaine (P = 0.83). We conclude that 0.5% levobupivacaine and 0.5% ropivacaine provide comparable surgical anesthesia and postoperative analgesia. IMPLICATIONS: No studies have compared the clinical properties of levobupivacaine with those of ropivacaine when providing sciatic nerve block for hallux valgus repair. Results from this prospective, randomized, double-blinded study demonstrate that 20 mL of either 0.5% levobupivacaine or 0.5% ropivacaine provide comparable surgical block with prolonged postoperative analgesia.

Adult↗