Ischemia and reperfusion (I/R) injury induced by tourniquet (TQ) application leads to the release of both oxygen free radicals and inflammatory cytokines. The skeletal muscle I/R may contribute to local skeletal muscle and remote organ damage affecting outcomes after total knee arthroplasty (TKA). The aim of the study is to summarize the current findings associated with I/R injury following TKA using a thigh TQ, which include cellular alterations and protective therapeutic interventions. The PubMed database was searched using the keywords “ischemia reperfusion injury,” “oxidative stress,” “tourniquet,” and “knee arthroplasty.” The search was limited to research articles published in the English language. Twenty-eight clinical studies were included in this qualitative review. Skeletal muscle I/R reduces protein synthesis, increases protein degradation, and upregulates genes in cell stress pathways. The I/R of the lower extremity elevates local and systemic oxidative stress as well as inflammatory reactions and impairs renal function. Propofol reduces oxidative injury in this I/R model. Ischemic preconditioning (IPC) and vitamin C may prevent oxygen free radical production. However, a high dose of N-acetylcysteine possibly induces kidney injury. In summary, TQ-related I/R during TKA leads to muscle protein metabolism alteration, endothelial dysfunction, oxidative stress, inflammatory response, and renal function disturbance. Propofol, IPC, and vitamin C show protective effects on oxidative and inflammatory markers. However, a relationship between biochemical parameters and postoperative clinical outcomes has not been validated.

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Both cerebral and cardiac ischemia causes loss of cerebral blood flow, which may lead to neuronal cell damage, neurocognitive impairment, learning and memory difficulties, neurological deficits, and brain death. Although reperfusion is required immediately to restore the blood supply to the brain, it could lead to several detrimental effects on the brain. Several studies demonstrate that microglia activity increases following cerebral and cardiac ischemic/reperfusion (I/R) injury. However, the effects of microglial activation in the brain following I/R remains unclear. Some reports demonstrated that microglia were involved in neurodegeneration and oxidative stress generation, whilst others showed that microglia did not respond to I/R injury. Moreover, microglia are activated in a time-dependent manner, and in a specific brain region following I/R. Recently, several therapeutic approaches including pharmacological interventions and electroacupuncture showed the beneficial effects, while some interventions such as hyperthermia and hyperoxic resuscitation, demonstrated the deteriorated effects on the microglial activity after I/R. Therefore, the present review summarized and discussed those studies regarding the effects of global and focal cerebral as well as cardiac I/R injury on microglia activation, and the therapeutic interventions.

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Trigeminal neuralgia (TN) is the neuropathic pain. Mitochondrial dysfunction, increased oxidative stress, and inflammation demonstrated in chronic pain. Carbamazepine (CBZ) is the first-line drug for TN, however, it is still insufficient. Coenzyme Q10 (CoQ10) has been used as the additional supplement for pain therapy. Nonetheless, mitochondrial respiratory proteins, oxidative stress, and inflammation in TN, and the add-on effects of CoQ10 on those defects have never been investigated. CBZ-treated TN-patients, naïve TN-patients, and control subjects were included. CBZ-treated TN-patients were randomised into two subgroups, received either CoQ10 or placebo for 2 months. Pain levels were evaluated, and peripheral blood mononuclear cells were isolated to determine the oxidative stress, mitochondrial oxidative phosphorylation (OXPHOS), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and cytokines including TNF-α, IL-1β and IL-18 mRNA expression. Pain scales, oxidative stress, and OXPHOS levels were greater in naïve TN-patients than control, whereas the cytokine profiles were unchanged. Although pain scales were lower in CBZ-treated TN-patients than in naïve TN-patients, oxidative stress, OXPHOS, and cytokine expression profiles were not different. PGC-1α levels found to be increased in CBZ-treated TN patients when compared with the naïve group. CoQ10 supplement in CBZ-treated TN patients reduced pain scale and oxidative stress and increased antioxidants levels when compared with placebo group. However, OXPHOS, PGC-1α, and cytokines were not different between groups. These findings suggest that increased oxidative stress could be potentially involved in the pathogenesis of TN. CoQ10 supplements can reduce oxidative stress, leading to more effective pain reduction in TN patients being treated with CBZ.

Background: Cardiac ischemia/reperfusion (I/R) injury induces brain damage through increased blood-brain barrier (BBB) breakdown, microglial hyperactivity, pro-inflammatory cytokines, amyloid-β deposition, loss of dendritic spines, brain mitochondrial dysfunction, and imbalanced mitochondrial dynamics. Previous studies demonstrated that mitochondrial fusion promoter reduced cardiac damage from cardiac I/R injury; however, following cardiac I/R injury, the roles of mitochondrial dynamics on the brain have not been investigated. Objective: To investigate the effects of pharmacological modulation using mitochondrial fusion promoter (M1) in the brain of rats following cardiac I/R injury. Methods: Twenty-four male Wistar rats were separated into two groups; 1) sham-operation (n = 8) and 2) cardiac I/R injury (n = 16). Rats in the cardiac I/R injury group were randomly received either normal saline solution as a vehicle or a mitochondrial fusion promoter (M1, 2 mg/kg) intravenously. Both treatments were given to the rats 15 minutes before cardiac I/R injury. At the end of the reperfusion protocol, the brain was rapidly removed to investigate brain mitochondrial function, mitochondrial dynamics proteins, microglial activity, and Alzheimer’s disease (AD) related proteins. Results: Cardiac I/R injury induced brain mitochondrial dynamics imbalance as indicated by reduced mitochondrial fusion proteins expression without alteration in mitochondrial fission, brain mitochondrial dysfunction, BBB breakdown, increased macrophage infiltration, apoptosis, and AD-related proteins. Pretreatment with M1 effectively increased the expression of mitofusin 2, a mitochondrial outer membrane fusion protein, reduced brain mitochondrial dysfunction, BBB breakdown, macrophage infiltration, apoptosis, and AD-related proteins in rats following cardiac I/R injury. Conclusion: This mitochondrial fusion promoter significantly protected rats with cardiac I/R injury against brain damage.

Tramadol hydrochloride/acetaminophen is a combination drug containing tramadol hydrochloride 37.5 mg and acetaminophen 325 mg. The use of 25% less tramadol in the combination product reduces the incidence of tramadol-related adverse events, while the addition of acetaminophen reduces the onset time of analgesia and improves the degree of analgesia. However, there was no clinically significant difference in the pharmacokinetic parameters of tramadol or acetaminophen when the fixed-dose combination was compared with the individual agents after multiple-dose administration. The onset time of tramadol hydrochloride/acetaminophen was the fastest at only 17 minutes compared 51 minutes for tramadol and 18 minutes for acetaminophen. This combination has been found to be effective in the management of postoperative pain. It improves pain relief and provides a faster onset and longer duration of action with fewer adverse events than either component separately. It also reduces the severity of pain, photophobia and phonophobia associated with migraine headache. Tramadol hydrochloride/acetaminophen has been shown to be most effective in patients with mild to moderate pain and has a lower risk of serious adverse events.

Patient: Male, 49 Final Diagnosis: Hiccups Symptoms: Hiccups Medication: Dexamethasone Clinical Procedure: Drug termination Specialty: General and Internal Medicine Objective: Adverse events of drug therapy Background: Hiccups induced by steroids administration is not common. Although it is not life-threatening and is always recognized as a transient and minor complication, it can be severely uncomfortable and significantly diminished patient quality of life. In this case report, persistent hiccups were observed in 2 middle-aged Thai men receiving low-dose intravenous dexamethasone. This case report highlights the awareness of severe dexamethasone-induced hiccups. Case Report: A 49-year-old man and a 38-year-old man were admitted to our hospital and received IV dexamethasone. The hiccups started after each patient received a single dose of dexamethasone. The frequency and severity of their hiccups increased over time during dexamethasone treatment. Hiccups still continued to occur despite the discontinuation of dexamethasone and lasted for 72 h after drug termination. Conclusions: Dexamethasone can cause persistent hiccups. Although hiccups are not life-threatening, it should not be neglected since it can be severely uncomfortable and significantly diminish patient quality of life. Termination of dexamethasone can gradually relieve hiccups. Dexamethasone should be used cautiously and clinicians must be aware of this undesirable effect.