Joint Receptors Research Articles

Joint receptors play a role in position sense after all!

Joint receptors play a role in position sense after all!

Thermoresponsive Polymeric Hydromorphone Prodrug Provides Sustained Local Analgesia without Apparent Adverse Effects.

The extensive use of opioids for chronic pain management has contributed significantly to the current opioid epidemic. While many alternative nonopioid analgesics are available, opioids remain the most potent analgesics for moderate to severe pain management. In addition to the implementation of multimodal analgesia, there is a pressing need for the development of more effective and safer opioids. In this study, we developed a thermoresponsive N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-based hydromorphone (HMP) prodrug (ProGel-HMP, HMP content = 16.2 wt %, in base form). The aqueous solution of ProGel-HMP was free-flowing at 4 °C but became a hydrogel when the temperature was raised to ≥37 °C, allowing sustained local retention when administered in vivo. When tested in the destabilization of the medial meniscus (DMM) mouse model of osteoarthritis (OA), ProGel-HMP was retained after intra-articular injection in the OA knee joint for at least 2 weeks postinjection, with low extra-articular distribution. ProGel-HMP was not detected in the central nervous system (CNS). A single dose of ProGel-HMP produced rapid and sustained joint pain resolution for greater than 14 days when compared to saline and dose-equivalent HMP controls, likely mediated through peripheral μ-opioid receptors in the knee joint. Systemic analgesia effect was absent in the DMM mice treated with ProGel-HMP, as evident in the lack of difference in tail flick response between the ProGel-HMP-treated mice and the controls (i.e., Healthy, Saline, and Sham). Repeated dosing of ProGel-HMP did not induce tolerance. Collectively, these data support the further development of ProGel-HMP as a potent, safe, long-acting and nonaddictive analgesic for better clinical pain management.

Effectiveness of Sensory Integration and Conventional Therapy on Impaired Kinesthesia in Peripheral Neuropathy

Background: Peripheral neuropathy is a result of damage to the nerves located outside of the brain and spinal cord. Over all prevalence in India varies from 5 - 2400 per 10,000 populations. Diabetic neuropathy is the most common type. Kinesthesia is the ability to sense the motion of a joint or limb. It is primarily influenced by muscle spindles and secondarily influenced by skin receptors and joint receptors. Objectives: To determine the effectiveness of sensory integration on kinesthesia in peripheral neuropathy and to compare the effect of sensory integration with conventional therapy on kinesthesia in peripheral neuropathy. Materials And Methods: This was an experimental study conducted on 68 subjects in which Group A received conventional therapy (control) and another group received sensory integration along with conventional therapy (experimental). Simple Random Sampling technique was used. Pre intervention assessment was done and treatment was given for 6 weeks. Post intervention assessment was done with help of outcome measures. Statistical analysis was done using students t test. Results: Among the 68 subjects, Group B which received sensory integration along with conventional therapy showed extremely significant improvement in impaired kinesthesia. In the Weber two point discrimination test, the post intervention comparison (8.6 with group A and 5.98 with group B) showed that group was extremely significant in improving joint position sense. In joint position sense for plantar flexion and dorsiflexion, Group B showed extremely proximate results to range which was asked and the range which was performed by the subjects. Conclusion: Sensory integration therapy was found to be significantly effective on impaired kinesthesia in peripheral neuropathy.

KO MAT2A to further inhibit hypomorphic PRMT5 in MATPdeficient TNBC cells for metastasis suppression in vitro and in vivo

Triple-negative breast cancer is one of the common types with the lack of three joint receptors, ER, PR, and HER2, which leads to inadequate responses for current breast cancer targeting therapy. Previous studies have reported that MTAP deletion confers enhanced sensitivity for PRMT5 inhibition, and inhibition of PRMT5 suppresses cell growth by decreasing arginine methylation of eIF4E and FGFR3. The KO of MAT2A will reduce the level of SAM, which is the substrate for arginine methylation, to inhibit PRMT5 and reduce cell proliferation. This study investigates the comparison of effects for MAT2A KO in MATP-deficient and MTAP+/+ TNBC cells in vivo and in vitro..

Inhibition of knee joint sensory afferents alters covariation across strides between quadriceps muscles during locomotion.

Sport-related injuries to articular structures often alter the sensory information conveyed by joint structures to the nervous system. However, the role of joint sensory afferents in motor control is still unclear. Here, we evaluate the role of knee joint sensory afferents in the control of quadriceps muscles, hypothesizing that such sensory information modulates control strategies that limit patellofemoreal joint loading. We compared locomotor kinematics and muscle activity before and after inhibition of knee sensory afferents by injection of lidocaine into the knee capsule of rats. We evaluated whether this inhibition reduced the strength of correlation between the activity of vastus medialis (VM) and vastus lateralis (VL) both across strides and within each stride, coordination patterns that limit net mediolateral patellofemoral forces. We also evaluated whether this inhibition altered correlations among the other quadriceps muscle activity, the time-profiles of individual EMG envelopes, or movement kinematics. Neither the EMG envelopes nor limb kinematics was affected by the inhibition of knee sensory afferents. This perturbation also did not affect the correlations between VM and VL, suggesting that the regulation of patellofemoral joint loading is mediated by different mechanisms. However, inhibition of knee sensory afferents caused a significant reduction in the correlation between vastus intermedius (VI) and both VM and VL across, but not within, strides. Knee joint sensory afferents may therefore modulate the coordination between the vasti muscles but only at coarse time scales. Injuries compromising joint afferents might result in altered muscle coordination, potentially leading to persistent internal joint stresses and strains.NEW & NOTEWORTHY Sensory afferents originating from knee joint receptors provide the nervous system with information about the internal state of the joint. In this study, we show that these sensory signals are used to modulate the covariations among the activity of a subset of vasti muscles across strides of locomotion. Sport-related injuries that damage joint receptors may therefore compromise these mechanisms of muscle coordination, potentially leading to persistent internal joint stresses and strains.

Effect of Selected Group of Asanas on the Patients with Cervical Vertigo

One of the most prevalent issues among patients in their middle years is vertigo. The existence of so-called cervical vertigo among the different causes of dizziness is still debatable. Based on the research of cervical vertigo was once believed to be caused by aberrant input from cervical sympathetic nerves. Later studies discovered that sympathetic stimulation has no effect on cerebral blood flow. Some studies made the hypothesis that diseases of vertigo of cervical origin can be associated to aberrant sensory input from the damaged joint receptors of upper cervical areas. Additional research revealed that cervical intervertebral disc disease appears to be the source of cervical vertigo. According to recent studies, vertigo of cervical origin may be associated to the in growth of many Ruffini corpuscles into degenerative cervical discs. Generally, the symptoms of Vertigo are not visible at the initial time, some time people consider it as epilepsy or brain related disease, first of all, it is necessary to diagnose and treat it properly. Yoga is an alternative therapy for any kind of cervical related problems, in which some special Asanas like Bhujangasana, Dhanurasana, Makarasana, Ardhamatsyendrasana, Akaranadhanurasana and Pranayama such as NadiShodhan, Bhramari, and Udgeetha. Which is helpful in this type of pain, it has been seen from many studies that yoga may work as a shield for spinal card related problems.

Understanding Athletic Trainers' Knowledge, Intervention, and Barriers Toward Arthrogenic Muscle Inhibition.

Arthrogenic muscle inhibition (AMI) is a common neurophysiological response to joint injury. While athletic trainers (ATs) are constantly treating patients with AMI, it is unclear how clinicians are using the available evidence to treat the condition. To investigate ATs' general knowledge, clinical practice, and barriers for treating AMI. A cross-sectional web-based survey was utilized. The survey was distributed to a random sample of 3000 ATs from the National Athletic Trainers' Association and through social media. 143 board certified ATs (age: 34.6 [10.3]y; experience: 11.7 [9.8]y) from various clinical settings and educational backgrounds were included in the analysis. One hundred one respondents were able to correctly identify the definition of AMI. The majority of these respondents correctly reported that joint effusion (n = 95, 94.1%) and abnormal activity from joint receptors (n = 91, 90.1%) resulted in AMI. Of the 101 respondents, only 58 (57.4%) reported using disinhibitory interventions to treat AMI. The most frequently used evidence supported interventions were transcutaneous electrical nerve stimulation (n = 38, 65.5%), neuromuscular electrical stimulation (n = 33, 56.9%), and focal joint cooling (n = 25, 43.1%). The interventions used correctly most often based on current evidence were neuromuscular electrical stimulation (n = 29/33, 87.9%) and transcutaneous electrical nerve stimulation (n = 26/38, 68.4%). Overall, difficulty quantifying AMI (n = 62, 61.24%) and lack of education (n = 71, 76.2%) were most frequently perceived as barriers. Respondents that did not use disinhibitory interventions perceived lack of experience treating AMI, understanding the terminology, and access to therapeutic modalities more often than the respondents that reported using disinhibitory interventions. Further education about concepts and treatment about AMI is warranted for ATs. Continued understanding of ATs' clinical practice in regard to AMI may help identify gaps in athletic training clinical education.

Expression and Correlation of IgG4 and IL-21 in Collagen-Induced Arthritis Rats.

PurposeWe explored the expression levels of IgG4 and interleukin (IL)-21 in the serum and ankle joints of collagen-induced arthritis (CIA) rats at different disease stages.Materials and MethodsWistar rats were randomly divided into normal and model groups, and the latter group was administered bovine type II collagen to induce arthritis. Enzyme-linked immunosorbent assay was performed at 21, 28, 35, and 42 days to detect IgG4 and IL-21 in the serum, followed by histological and immunohistochemical analyses of IgG4 and IL-21r in the ankle joint of rats.ResultsThe contents of IgG4 and IL-21 in the serum of the CIA model group were positively correlated and increased with disease progression. The expression of IgG4 and IL-21 receptors in the ankle joint of the CIA model group was significantly higher than that in the control group. These proteins were closely related to the pathological score. The serum IL-21 level in the model group was closely related to the level of IL-21 receptor in the ankle joint.ConclusionIL-21 may promote the occurrence and development of rheumatoid arthritis by combining with IL-21r to regulate the content of IgG4.

Drug Delivery Systems for the Treatment of Knee Osteoarthritis: A Systematic Review of In Vivo Studies.

Many efforts have been made in the field of nanotechnology to improve the local and sustained release of drugs, which may be helpful to overcome the present limitations in the treatment of knee OA. Nano-/microparticles and/or hydrogels can be now engineered to improve the administration and intra-articular delivery of specific drugs, targeting molecular pathways and pathogenic mechanisms involved in OA progression and remission. In order to summarize the current state of this field, a systematic review of the literature was performed and 45 relevant studies were identified involving both animal models and humans. We found that polymeric nanoparticles loaded with anti-inflammatory drugs (i.e., dexamethasone or celecoxib) are the most frequently investigated drug delivery systems, followed by microparticles and hydrogels. In particular, the nanosystem most frequently used in preclinical research consists of PLGA-nanoparticles loaded with corticosteroids and non-steroidal anti-inflammatory drugs. Overall, improvement in histological features, reduction in joint inflammation, and improvement in clinical scores in patients were observed. The last advances in the field of nanotechnology could offer new opportunities to treat patients affected by knee OA, including those with previous meniscectomy. New smart drug delivery approaches, based on nanoparticles, microparticles, and hydrogels, may enhance the therapeutic potential of intra-articular agents by increasing the permanence of selected drugs inside the joint and better targeting specific receptors and tissues.

Targeted therapy of rheumatoid arthritis via macrophage repolarization

The polarization of macrophages plays a critical role in the physiological and pathological progression of rheumatoid arthritis (RA). Activated M1 macrophages overexpress folate receptors in arthritic joints. Hence, we developed folic acid (FA)-modified liposomes (FA-Lips) to encapsulate triptolide (TP) (FA-Lips/TP) for the targeted therapy of RA. FA-Lips exhibited significantly higher internalization efficiency in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells than liposomes (Lips) in the absence of folate. Next, an adjuvant-induced arthritis (AIA) rat model was established to explore the biodistribution profiles of FA-Lips which showed markedly selective accumulation in inflammatory paws. Moreover, FA-Lips/TP exhibited greatly improved therapeutic efficacy and low toxicity in AIA rats by targeting M1 macrophages and repolarizing macrophages from M1 to M2 subtypes. Overall, a safe FA-modified liposomal delivery system encapsulating TP was shown to achieve inflammation-targeted therapy against RA via macrophage repolarization.

Topography of sensory receptors within the human glenohumeral joint capsule

Sensory receptors in the joint capsule are critical for maintaining joint stability. However, the distribution of sensory receptors in the glenohumeral joint of the shoulder, including mechanoreceptors and free nerve endings, has not been described yet. This study aimed to describe the distributions of different sensory receptor subtypes in the glenohumeral joint capsule. Our hypotheses were as follows: (1) Sensory receptor subtypes would differ in density but follow a similar distribution pattern, and (2) the anterior capsule would have the highest density of sensory receptors. Six glenohumeral joint capsules were harvested from the glenoid to the humeral attachment. The capsule was divided into 4 regions of interest(anterior, posterior, superior, and inferior) and analyzed using modified gold chloride stain. Sensory receptors as well as free nerve endings were identified and counted under a light microscope from sections of each region of interest. The density of each sensory receptor subtype was calculated relative to capsule volume. Sensory receptors were distributed in the glenohumeral joint capsule with free nerve endings. The anterior capsule exhibited the highest median density of all 4 sensory receptors examined, followed by the superior, inferior, and posterior capsules. The median densities of these sensory receptor subtypes also significantly differed (P = .007), with type I (Ruffini corpuscles) receptors having the highest density (2.97 U/cm3), followed by type IV (free nerve endings, 2.25 U/cm3), type II (Pacinian corpuscles, 1.40 U/cm3), and type III (Golgi corpuscles, 0.24 U/cm3) receptors. Sensory receptor subtypes are differentially expressed in the glenohumeral joint capsule, primarily type I and IV sensory receptors. The expression of sensory receptors was dominant in the anterior capsule, stressing the important role of proprioception feedback for joint stability. The surgical procedure for shoulder instability should consider the topography of sensory receptors to preserve or restore the proprioception of the shoulder joint.

Craniomandibular Disorders in Pregnant Women: An Epidemiological Survey.

Temporomandibular joint (TMJ) disorder has been reported to be 1.5 to two times more common in women than men. Such a gender-based difference could be attributed to behavioral, hormonal, anatomical, and psychological characteristics. Physiological hormonal differences between genders could be one of the possible explanations for the higher incidence of temporomandibular disorder (TMD) in women. As the plasma level of certain female hormones increases during gestation, it could be assumed that there is a higher prevalence of dysfunctional signs and symptoms in pregnant women. We performed an epidemiological survey based on screening for TMD in a group of 108 pregnant women and found that 72% of young women reported significant signs of TMJ disorders, 9% of the young women reported mild signs of TMJ disorders, and 19% of the included subjects reported no signs or symptoms of TMD. The presence of estrogen receptors in the temporomandibular joint of female baboons could be the basis of an explanation for the increased prevalence of dysfunction in young women reported in the literature and the high feedback we have seen of joint noises in pregnant women. On the basis of the present findings, it could be assumed that gestation period could represent a risk factor for craniomandibular dysfunctions.

The association between high levels of luteinizing hormone and proliferative retinopathy of prematurity in female preterm infants

BackgroundLuteinizing hormone (LH) and human chorionic gonadotropin (hCG), generally considered reproductive hormones, have potent proangiogenic properties. Both of these hormones and their joint receptor (CG/LH receptor) are found in the human eye. We hypothesized that an excess of these hormones is associated with proliferative retinopathy of prematurity (P-ROP). MethodsDried blood spots (DBS) were used to perform a cross-sectional study of infants (gestational age of <26 weeks) with and without P-ROP, born in Michigan between August 1, 2012, and March 15, 2015. The DBS were collected at 1 week and 4 weeks of age from 45 preterm infants (27 no-ROP and 18 P-ROP). The DBS were linked to hospital records and then deidentified. ICD-9 codes were used to identify P-ROP cases. Hormones levels were measured via electrochemiluminescence assays on the Meso Scale Discovery platform. Associations between hormone levels at 1 and 4 weeks of age and the presence or absence of P-ROP were assessed. ResultsIn female infants, we noted a trend toward higher LH levels in ROP cases at week 1 (P = 0.11) and significantly higher LH levels in cases at week 4 (P = 0.03). In male infants, no ROP-related differences in LH levels were found at either time point. For hCG levels, no associations with P-ROP were found in either sex at either time point. ConclusionsThe association of high LH with P-ROP in female but not male infants raises the possibility that there are sex-specific hormonal determinants of aberrant retinal angiogenesis.

Cerebellar Transcranial Magnetic Stimulation Disrupts Vestibular Reflexes in Standing Balance

Despite its seemingly effortless execution, standing balance is a complex task maintained by the integration of sensory feedback from visual, somatosensory (muscle, skin, joint receptors), and vestibular (inner ear) systems. The vestibular system provides feedback about head acceleration and can be manipulated experimentally by passing an electrical current percutaneously through the mastoid processes. The cerebellum plays an important role in standing balance by integrating sensory feedback to refine activity in postural muscles. A recent study has shown that experimentally depressing cerebellar activity with repetitive transcranial magnetic stimulation can influence postural sway and muscle reflex responses following electrical vestibular stimulation. The aim of this study was to investigate the impact of acute cerebellar stimulation on vestibular muscle reflex responses in different head positions during standing balance. We applied a novel combination of stochastic electrical vestibular stimulation (SVS, ±2.5 mA, 0–20 Hz) and single‐pulse cerebellum transcranial magnetic stimulation (TMS, 60% maximum stimulator output) on fifteen healthy adults (6 males, 9 females; 21–32 years old) in two head positions: head forward and head right. Muscle reflexes were recorded bilaterally with surface electromyography (EMG) from lower leg (soleus and medial gastrocnemius) and neck (sternocleidomastoid) muscles. Time‐based cumulant density and frequency‐based coherence analyses were used to evaluate the relationship between the SVS and evoked EMG responses one second before (Pre) and one second after (Post) cerebellar TMS. 50 TMS pulses were delivered per head position. Preliminary analysis performed on left medial gastrocnemius (LMG) head right data indicated a significant reduction in the short latency (SL, P = 0.0377) and medium latency (ML, P &lt; 0.0001) reflexes following cerebellar TMS (Fig. 1). In addition, a significant drop in the coherence between the SVS and LMG Pre to Post was found using a difference of coherence test. These findings support the cerebellum to be an important center for the integration of vestibular feedback for the control of standing balance.Support or Funding InformationMount Royal University Faculty of Science and TechnologyFigure 1

Investigation of salmon calcitonin in regulating fibrosis-related molecule production and cell-substrate adhesion in frozen shoulder synovial/capsular fibroblasts.

The purpose of this study was to evaluate the effect of salmon calcitonin (sCT) on improving fibrosis-related indicators in frozen shoulder synovial/capsular fibroblasts (SCFs) and detect the potential downstream pathway. Quantitative real-time polymerase chain reaction and cell-substrate adhesion assays were used to measure alterations in fibrosis-related molecule expression and the cell adhesion ability of frozen shoulder SCFs after treatment with range concentrations of sCT. The presence of calcitonin receptors (CTRs) in shoulder joint synovial/capsular tissue samples was detected by immunohistochemistry (IHC). The downstream pathways of sCT in SCFs were further explored by utilizing three classical pathway inhibitors. With the addition of sCT to the culture medium of frozen shoulder SCFs, the messenger RNA (mRNA) expression of collagen type I (COL1A1), COL3A1, fibronectin 1, laminin 1, transforming growth factor-β1 (TGF-β1), and interleukin-1α (IL-1α) showed a descending trend as the sCT concentration increased. Treatment with sCT increased the expression of vascular endothelial growth factor and IL-6 in a dose-dependent manner. The enhanced adhesion ability of frozen shoulder SCFs gradually diminished with increasing concentrations of sCT. By using IHC, the CTR was detected extensively in the frozen shoulder joint synovium and capsule. Blocking the protein kinase C (PKC) pathway reversed the sCT-mediated suppression of COL1A1 production. Blocking the PKC or protein kinase A (PKA) pathway eliminated the sCT-induced inhibition of TGF-β1 production. This study demonstrated that sCT effectively improved the mRNA expression of fibrosis-related molecules and decreased the enhanced cell-substrate adhesion ability of frozen shoulder SCFs. sCT might achieve these effects by interacting with the CTR that is expressed on the SCF surface and by activating the downstream PKC or PKA pathway.

Effects of task dynamics on coordination of the hand muscles and their adaptation to targeted muscle assistance

Dynamic characteristics of a manual task can affect the control of hand muscles due to the difference in biomechanical/physiological characteristics of the muscles and sensory afferents in the hand. We aimed to examine the effects of task dynamics on the coordination of hand muscles, and on the motor adaptation to external assistance. Twenty-four healthy subjects performed one of the two types of a finger extension task, isometric dorsal fingertip force production (static) or isokinetic finger extension (dynamic). Subjects performed the tasks voluntarily without assistance, or with a biomimetic exotendon providing targeted assistance to their extrinsic muscles. In unassisted conditions, significant between-task differences were found in the coordination of the extrinsic and intrinsic hand muscles, while the extrinsic muscle activities were similar between the tasks. Under assistance, while the muscle coordination remained relatively unaffected during the dynamic task, significant changes in the coordination between the extrinsic and intrinsic muscles were observed during the static task. Intermuscular coherence values generally decreased during the static task under assistance, but increased during the dynamic task (all p-values < 0.01). Additionally, a significant change in the task dynamics was induced by assistance only during static task. Our study showed that task type significantly affect coordination between the extrinsic and intrinsic hand muscles. During the static task, a lack of sensory information from musculotendons and joint receptors (more sensitive to changes in length/force) is postulated to have resulted in a neural decoupling between muscles and a consequent isolated modulation of the intrinsic muscle activity.

Correlation of core muscles endurance and balance in subjects with osteoarthritis knee

Background: Osteoarthritis (OA) is a chronic degenerative joint disease with a prevalence of about 29% in India. Reduced kinesthetic receptors in joint especially around the ligaments in the knee can lead to impaired proprioceptive information to an individual. Core muscle endurance deficiency leads to an increase in the loading of the knee, as well as in knee joint contact force during dynamic movement. Hence, poor core stability may be one of the contributing factors that lead to knee OA development as well as its progression. Objectives: The objective of this study was to find a correlation between core muscle endurance and balance in subjects with OA. Material and Methods: The observational study was conducted on 50 healthy, male and female subjects, age >40 years diagnosed with OA knee using convenience sampling. Subjects underwent core stability assessment consisting of plank, bilateral side bridge, Sorenson, and 60-degree trunk flexion endurance tests. Y-balance test -Lower quarter (YBT-LQ) was used to measure dynamic balance in individuals. The data were analyzed at a 5% level of significance using SPSS. Outcomes were correlated using Spearman’s correlation of coefficient. Results: Correlation was found between YBT-LQ and plank r = 0.402 (P = 0.004), YBT-LQ and right side bridge 0.425 (P = 0.002), YBT-LQ and left side bridge r = 0.490 (P = 0.001), YBT-LQ and 60° trunk flexion test r = 0.369 (P = 0.008), and YBT-LQ and Sorenson test r = 0.324 (P = 0.022). Conclusion: There is a weak to moderate correlation between core endurance and balance in subjects with OA knee.

Hyperglycosylated hCG Drives Malignancy in Most or All Human Cancers: Tying All Research Together

Objectives: Two forms of hCG are produced, the hormone hCG binding a luteinizing hormone/hCG joint receptor and the autocrine hyperglycosylated hCG binding a TGF-ß receptor. In pregnancy, hyperglycosylated hCG drives placental cell growth and invasion in implantation of pregnancy. It also blocks apoptosis. Human cancer cells steal the hCG ß-subunit gene and use hyperglycosylated hCG and its ß-subunit to drive malignancy. Here we examine research into hyperglycosylated hCG and its ß-subunit, and show that these molecules drive malignancy in most or possibly all human cancers. Methods: Mouse monoclonal antibody B152was raised against intact hyperglycosylated hCG, batch C5. The antibody binds hyperglycosylated hCG and its ß-subunit but does not bind the hormone hCG or its subunits. Total hCG was measured using the Siemens Immulite hCG assay, hyperglycosylated hCG and its ß-subunit were measured using the antibody B152 assay. Results: Eight independent center show that the hCG ß-subunit produced by cancers promotes malignancy, enhances cancer cell growth, cancer cell invasion and blockage of apoptosis in cancers. A study of 42 choriocarcinoma cases shows that percentage hyperglycosylated hCG exactly correlates with weekly doubling rate of cancer. It is concluded that hyperglycosylated hCG drive malignancy in this cancer. In a study with 7 separate cancers it is shown that increasing concentrations of hyperglycosylated hCG enhance all cancers. Increasing concentration of monoclonal antibody B152. Hyperglycosylated hCG and its ß-subunit drives cancer growth, cancer invasion and blocks apoptosis in cancer cells. Antibody B152 suppressed cancer cell growth creating a non-malignant-like state (no growth, no invasion), with no cancer growth over a starting 70% confluency. Conclusions: Choriocarcinoma is an example of cancer driven in malignancy by hyperglycosylated hCG, cancer aggression (weekly doubling rate) exactly correlating with percent hyperglycosylated hCG. In examining cancers, antibody B152 suppresses malignancy totally halting cancer growth in 7 of 7 cancer. This confirms that only the antigens, hyperglycosylated hCG and its ß-subunit drives malignancy in cancer cases.

Neuroanatomical distribution of sensory receptors in the human elbow joint capsule.

The topographic arrangement of sensory receptors in the human elbow joint capsule is pertinent to their role in the transmission of neural signals. The signals from stimuli in the joint are concisely delivered via afferent pathways to allow recognition of pain and proprioception. Sensory receptors in the elbow joint include mechanoreceptors and free nerve endings acting as nociceptors, although the distribution of each of the structures has not been determined, despite their importance for the integrity of the joint. We therefore aimed to investigate the neuroanatomical distribution and densities of mechanoreceptors and free nerve endings in the capsule of the elbow, at the same time as considering surgical approaches that would result in the minimum insult to them. Four elbow joint capsules were harvested from fresh cadavers. The specimens were carefully separated from adjacent osteoligamentous attachments and the capsular complex was stained with a modified gold chloride method. Evaluations of free nerve endings, and Golgi, Ruffini and Pacinian corpuscles were performed under an inverted light microscope. The number and density of each structure were recorded. Ruffini corpuscles observed to be the dominant mechanoreceptor type. No Golgi corpuscle was observed. Free nerve endings were found at the highest density at posterodistal sites, whereas mechanoreceptors were most frequent at bony attachment sites. A consistent distribution pattern of articular sensory receptors was observed, which allows further understanding of elbow pathology. An awareness of the neuroanatomical distribution of sensory receptors in the elbow joint capsule may allow their preservation during surgical procedures for elbow joint pathology.

Cervical Vertigo: Historical Reviews and Advances.

Vertigo is one of the most common presentations in adult patients. Among the various causes of vertigo, so-called cervical vertigo is still a controversial entity. Cervical vertigo was first thought to be due to abnormal input from cervical sympathetic nerves based on the work of Barré and Liéou in 1928. Later studies found that cerebral blood flow is not influenced by sympathetic stimulation. Ryan and Cope in 1955 proposed that abnormal sensory information from the damaged joint receptors of upper cervical regions may be related to pathologies of vertigo of cervical origin. Further studies found that cervical vertigo seems to originate from diseased cervical intervertebral discs. Recent research found that the ingrowth of a large number of Ruffini corpuscles into diseased cervical discs may be related to vertigo of cervical origin. Abnormal neck proprioceptive input integrated from the signals of Ruffini corpuscles in diseased cervical discs and muscle spindles in tense neck muscles secondary to neck pain is transmitted to the central nervous system and leads to a sensory mismatch with vestibular and other sensory information, resulting in a subjective feeling of vertigo and unsteadiness. Further studies are needed to illustrate the complex pathophysiologic mechanisms of cervical vertigo and to better understand and manage this perplexing entity.