Hydroxyapatite, (HA; Ca1O(PO4)6(OH)2) has been successfully applied in medical and dental applications for several years due to its excellent biocompatibility. The usage of HA in Malaysia, however, is limited due to the lack of availability. Therefore the aim of this work is to produce HA materials from both pure chemicals and from Malaysian natural limestone precursors, and to compare their bulk properties. However, parts of Malaysian natural limestone deposits actually consist of a combination of Ca(OH)2 and CaCO3. In order to utilise the limestone to produce HA material, the combination of these commercially pure chemicals as HA precursors should still work. In order to test this hypothesis, two HAs were produced by wet synthesis technique utilising (a) combination of Ca(OH)2 + CaCO3 from pure commercial chemicals [WCC] and (b) a local natural limestone [WL] precursors. The HAs produced; WCC and WL, were compacted into discs and sintered at 1250 degrees C. The characterisations and evaluations conducted were XRD, SEM-EDX, FTIR and shrinkage factor. The results indicate that WL gives slightly better bulk properties compared to WCC.
Sjogren's syndrome B antibody ; MALAYSIAN ; hydroxyl group ; Calcium measurement ; Work

BACKGROUND: Pregabalin is an analog of gamma aminobutyric acid, and selectively interacts with the alpha-2-delta subunit of the voltage dependent calcium channels. The aims of this study were to investigate the analgesic effects of intrathecal pregabalin in rat formalin tests and to compare between the pre-treatment and post-treatment group. METHODS: All experimental animals were randomly divided into pre- and post-treatment groups. In pre-treatment groups, pregabalin (0.003g, 0.01g, 0.03g, 0.1g, n = 6 at each group) was administered through the intrathecal catheter 10 min prior to formalin injection. In post-treatment groups, pregabalin (0.01g, 0.03g, 0.1g, 0.3g, n = 6 at each group) was administered through the catheter 10 min after formalin injection. Formalin (50 ml, 5%) was injected in the left hind paw. We counted the number of flinching as a pain behavior for 60 min to quantify the nociceptive response. RESULTS: The withdrawal responses which were represented by flinching count, were decreased dose dependently in the phase 2, in all groups (pre-treatment and post-treatment group), while there were less analgesic effects and ceiling effects in the phase 1. There was more significant decreasing flinching number in the pre-treatment group than that in the post-treatment group. CONCLUSIONS: Intrathecal pregabalin has preemptive analgesic effect and may be useful in the management of inflammation induced hyperalgesia.
Animals ; Calcium Channels ; Catheters ; Formaldehyde* ; gamma-Aminobutyric Acid ; Hyperalgesia ; Inflammation ; Pain Measurement* ; Rats* ; Pregabalin

Voltage dependent calcium channel (VDCC), one of the most important regulator of Ca2+ concentration in neuron, play an essential role in the central processing of nociceptive information. The present study investigated the antinociceptive effects of L, T or N type VDCC blockers on the formalin-induced orofacial inflammatory pain. Experiments were carried out on adult male Sprague-Dawley rats weighing 220-280 g. Anesthetized rats were individually fixed on a stereotaxic frame and a polyethylene (PE) tube was implanted for intracisternal injection. After 72 hours, 5% formalin (50 microL) was applied subcutaneously to the vibrissa pad and nociceptive scratching behavior was recorded for nine successive 5 min intervals. VDCC blockers were administered intracisternally 20 minutes prior to subcutaneous injection of formalin into the orofacial area. The intracisternal administration of 350 or 700 microg of verapamil, a blocker of L type VDCC, significantly decreased the number of scratches and duration in the behavioral responses produced by formalin injection. Intracisternal administration of 75 or 150 microg of mibefradil, a T type VDCC blocker, or 11 or 22 microg of cilnidipine, a N type VDCC blocker, also produced significant suppression of the number of scratches and duration of scratching in the first and second phase. Neither intracisternal administration of all VDCC blockers nor vehicle did not affect in motor dysfunction. The present results suggest that central VDCCs play an important role in orofacial nociceptive transmission and a targeted inhibition of the VDCCs is a potentially important treatment approach for inflammatory pain originating in the orofacial area.
Adult ; Animals ; Calcium ; Calcium Channel Blockers ; Calcium Channels ; Calcium Channels, L-Type ; Calcium Channels, N-Type ; Calcium Channels, T-Type ; Dihydropyridines ; Facial Pain ; Formaldehyde ; Humans ; Injections, Subcutaneous ; Male ; Mibefradil ; Neurons ; Pain Measurement ; Polyethylene ; Rats ; Rats, Sprague-Dawley ; Verapamil

BACKGROUND: Gabapentin is thought to exert an effect through the voltage-dependent calcium channel. Vitamin E is a widely known antioxidant which neutralizes the harmful effect of ROS which is considered to play a prominent role in various painful conditions. This study was therefore conducted to assess the antinociceptive effects of gabapentin and vitamin E and the interaction of these drugs in the modulation of pain in rats subjected to a formalin test. METHODS: Sprague-Dawley rats with a lumbar intrathecal catheter were tested for their paw flinches by 5% formalin injection after intrathecal injection of gabapentin or vitamin E. After obtaining dose-response curves for each drug, the effect of the combination was tested by the total dose fraction value and isobolographic analysis. RESULTS: When a single drug was injected intrathecally, significant dose-dependent decreases in flinches were shown only in the late phase. ED50 values of intrathecal gabapentin and vitamin E in the late phase were 75.3 +/- 9.58 microg, and 17.56 +/- 1.65 mg/kg respectively. The combination of gabapentin and vitamin E produced dose-dependent decreases in the number of flinches in both phases induced by the formalin test. The ED50 value of the combination was lower than the theoretical additive values in the late phase, but did not show a significant difference with the theoretical additive value. CONCLUSIONS: Gabapentin and vitamin E (by itself) have no antinociceptive effect in the early phase; however their combination has shown an antinociceptive effect. In addition, they show additive effects in the late phase of the formalin test.
Amines ; Animals ; Calcium Channels ; Catheters ; Cyclohexanecarboxylic Acids ; Drug Interactions ; Formaldehyde ; gamma-Aminobutyric Acid ; Injections, Spinal ; Pain Measurement ; Rats ; Rats, Sprague-Dawley ; Vitamin E ; Vitamins

OBJECTIVETo evaluate the efficacy of conservative treatment with teriparatide for promoting bone fracture healing in patients with osteoporotic vertebral fracture.

METHODSTwelve postmenopausal patients (aged 73±4.8 years) with osteoporotic spinal fracture confirmed by MRI or CT scanning received conservative treatment with teriparatidesc injection supplemented with calcium and analgesics for 6 months. At the beginning and at the end of the therapy, VAS score, Oswestry Disability Index (ODI), bone mass densitometry, and X-ray of the thoracic and lumbar spine, and serum P1NP and beta-CTX levels were measured. Six of the patients received a second MRI scan after the therapy to evaluate the bone healing.

RESULTSAll the 12 patients completed the treatment, during which no new fractures or adverse events occurred. At the end of the first month of treatment, analgesic was withdrawn for all the patients. The average VAS score decreased from 8±2 to 1±2 at 1 month during the therapy, and ODI was reduced from (76±12)% to (20±5)% at 1 month and further to (5±4)% at 6 month. After the 6-month therapy, the height of the fractured vertebrae (presented as the anterior to posterior wall height ratio) was insignificantly decreased from (75±20)% to (61±20)%, the BMD was increased by (20±5)%, P1NP increased significantly from 20.9±11.4 ng/mL to 80.0±41.2 ng/mL, and beta-CTX increased from 0.30±0.17 ng/mL to 0.51±0.3 ng/mL. The 6 patients re-examined with MRI demonstrated complete bone healing after the therapy.

CONCLUSIONTeriparatide is effective for conservative treatment of osteoporotic spinal fracture and can promote bone fracture healing, improve the quality of life, and prevents vertebral collapse, and can be therefore an alternative treatment to PVP or BV.

Aged ; Analgesics ; therapeutic use ; Bone Density ; Calcium ; therapeutic use ; Fractures, Compression ; drug therapy ; Humans ; Lumbar Vertebrae ; pathology ; Magnetic Resonance Imaging ; Osteoporotic Fractures ; drug therapy ; Pain Measurement ; Quality of Life ; Spinal Fractures ; drug therapy ; Teriparatide ; therapeutic use ; Treatment Outcome

Sildenafil increases the cyclic guanosine monophosphate (cGMP) by inhibition of a phosphodiesterase 5, thereby leading to an antinociceptive effect. The increased cGMP may exert the effect on an L-type calcium channel through the activation of protein kinase G (PKG). The purpose of this study was to examine the possible involvement of a PKG-L-type calcium channel on the effect of sildenafil at the spinal level. Catheters were inserted into the intrathecal space of male SD rats. Pain was induced by applying 50 microliter of a 5% formalin solution to the hindpaw. The sildenafil-induced effect was examined after an intrathecal pretreatment of a PKG inhibitor (KT 5823), or a L-type calcium channel activator (FPL 64176). Intrathecal sildenafil produced an antinociceptive effect during phase 1 (0~10 min interval) and phase 2 (10~60 min interval) in the formalin test. Intrathecal KT 5823 and FPL 64176 attenuated the antinociceptive effect of sildenafil during both phases. Sildenafil is effective against both acute pain and the facilitated pain state at the spinal level. In addition, the inhibition of an L-type calcium channel by activation of the PKG may contribute to the antinocieptive mechanism of sildenafil in the spinal cord.
Animals ; Calcium Channel Agonists/pharmacology ; Calcium Channels, L-Type/*physiology ; Carbazoles/pharmacology ; Cyclic GMP-Dependent Protein Kinases/antagonists & inhibitors/*physiology ; Dose-Response Relationship, Drug ; Male ; Pain/drug therapy/*physiopathology ; Pain Measurement ; Piperazines/*pharmacology/therapeutic use ; Protein Kinase Inhibitors/pharmacology ; Purines/pharmacology/therapeutic use ; Pyrroles/pharmacology ; Rats ; Rats, Sprague-Dawley ; Sulfones/*pharmacology/therapeutic use

This study was designed to determine whether early gabapentin treatment has a protective analgesic effect on neuropathic pain and compared its effect to the late treatment in a rat neuropathic model, and as the potential mechanism of protective action, the alpha2delta1-subunit of the voltage-dependent calcium channel (alpha2delta1-subunit) was evaluated in both sides of the L5 dorsal root ganglia (DRG). Neuropathic pain was induced in male Sprague-Dawley rats by a surgical ligation of left L5 nerve. For the early treatment group, rats were injected with gabapentin (100 mg/kg) intraperitoneally 15 min prior to surgery and then every 24 hr during postoperative day (POD) 1-4. For the late treatment group, the same dose of gabapentin was injected every 24 hr during POD 8-12. For the control group, L5 nerve was ligated but no gabapentin was administered. In the early treatment group, the development of allodynia was delayed up to POD 10, whereas allodynia was developed on POD 2 in the control and the late treatment group (p<0.05). The alpha2delta1-subunit was up-regulated in all groups, however, there was no difference in the level of the alpha2delta1-subunit among the three groups. These results suggest that early treatment with gabapentin offers some protection against neuropathic pain but it is unlikely that this action is mediated through modulation of the alpha2delta1-subunit in DRG.
Amines/administration & dosage/*therapeutic use ; Analgesics/administration & dosage/*therapeutic use ; Animals ; Calcium Channels/genetics/*metabolism ; Cyclohexanecarboxylic Acids/administration & dosage/*therapeutic use ; Disease Models, Animal ; Injections, Intraperitoneal ; Ligation ; Male ; Neuralgia/*drug therapy/metabolism ; Pain Measurement ; Protein Subunits/genetics/metabolism ; Rats ; Rats, Sprague-Dawley ; Spinal Nerves/surgery ; Up-Regulation ; gamma-Aminobutyric Acid/administration & dosage/*therapeutic use